Effect of a Strategy of Comprehensive Vasodilation vs Usual Care on Mortality and Heart Failure Rehospitalization Among Patients With Acute Heart Failure: The GALACTIC Randomized Clinical Trial.

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.

Ability of a 24-h ambulatory cuffless blood pressure monitoring device to track blood pressure changes in clinical practice.

OBJECTIVE: There is an increasing number of cuffless blood pressure (BP) measurement (BPM) devices. Despite promising results when comparing single measurements, the ability of these devices to track changes in BP levels over 24 h related to an initial calibration BP (CalibBP) is unknown. Our aim was to analyse this ability in a cuffless device using pulse transit time. METHODS: We prospectively enrolled 166 participants for simultaneously performed cuffless (Somnotouch-NIBP) and cuff-based (Spacelabs 90217A/IEM Mobil-O-graph) 24 h BPM. As CalibBP for the cuffless device, first cuff-based BP was used. As surrogate for changes in BP levels after the CalibBP, we used the difference between the CalibBP and mean 24 h, awake and asleep BP measured by the two devices. In addition, we analysed the relationship between the difference of the CalibBP and the cuff-based BPM versus the difference between the cuff-based and the cuffless BPM devices. RESULTS: Mean(SD) difference between the CalibBP and mean 24hBP by the cuff-based or cuffless BP device were 7.4 (13.2) versus 1.8 (8.3) mmHg for systolic ( P  < 0.0001) and 6.6 (6.8) versus 1.6 (5.8) mmHg for diastolic ( P  < 0.0001). A near linear relationship was seen among the difference between the CalibBP and the cuff-based BPM values and the difference between the cuff-based and cuffless BPM device. CONCLUSION: Our data indicate a lower ability of the cuffless BPM device to track changes of BP levels after CalibBP. In addition, cuffless device accuracy was associated with the changes in BP levels after the initial CalibBP - the larger the BP level change, the larger the difference between the devices. REGISTRATION: https://www.clinicaltrials.gov ; Unique identifier: NCT03054688; NCT03975582.

Management of hypertensive disorders in pregnancy: a Position Statement of the European Society of Hypertension Working Group 'Hypertension in Women'.

Hypertensive disorders in pregnancy (HDP), remain the leading cause of adverse maternal, fetal, and neonatal outcomes. Epidemiological factors, comorbidities, assisted reproduction techniques, placental disorders, and genetic predisposition determine the burden of the disease. The pathophysiological substrate and the clinical presentation of HDP are multifarious. The latter and the lack of well designed clinical trials in the field explain the absence of consensus on disease management among relevant international societies. Thus, the usual clinical management of HDP is largely empirical. The current position statement of the Working Group 'Hypertension in Women' of the European Society of Hypertension (ESH) aims to employ the current evidence for the management of HDP, discuss the recommendations made in the 2023 ESH guidelines for the management of hypertension, and shed light on controversial issues in the field to stimulate future research.

Quantifying Hemodynamic Cardiac Stress and Cardiomyocyte Injury in Normotensive and Hypertensive Acute Heart Failure.

BACKGROUND: The characterization of the different pathophysiological mechanisms involved in normotensive versus hypertensive acute heart failure (AHF) might help to develop individualized treatments. METHODS: The extent of hemodynamic cardiac stress and cardiomyocyte injury was quantified by measuring the B-type natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP), and high-sensitivity cardiac troponin T (hs-cTnT) concentrations in 1152 patients presenting with centrally adjudicated AHF to the emergency department (ED) (derivation cohort). AHF was classified as normotensive with a systolic blood pressure (SBP) of 90-140 mmHg and hypertensive with SBP > 140 mmHg at presentation to the ED. Findings were externally validated in an independent AHF cohort (n = 324). RESULTS: In the derivation cohort, with a median age of 79 years, 43% being women, 667 (58%) patients had normotensive and 485 (42%) patients hypertensive AHF. Hemodynamic cardiac stress, as quantified by the BNP and NT-proBNP, was significantly higher in normotensive as compared to hypertensive AHF [1105 (611-1956) versus 827 (448-1419) pg/mL, and 5890 (2959-12,162) versus 4068 (1986-8118) pg/mL, both p < 0.001, respectively]. Similarly, the extent of cardiomyocyte injury, as quantified by hs-cTnT, was significantly higher in normotensive AHF as compared to hypertensive AHF [41 (24-71) versus 33 (19-59) ng/L, p < 0.001]. A total of 313 (28%) patients died during 360 days of follow-up. All-cause mortality was higher in patients with normotensive AHF vs. patients with hypertensive AHF (hazard ratio 1.66, 95%CI 1.31-2.10; p < 0.001). Normotensive patients with a high BNP, NT-proBNP, or hs-cTnT had the highest mortality. The findings were confirmed in the validation cohort. CONCLUSION: Biomarker profiling revealed a higher extent of hemodynamic stress and cardiomyocyte injury in patients with normotensive versus hypertensive AHF.

Reply to Hungerford, S.; Bart, N. Blood-Pressure-Monitoring Smartphone Applications: Ushering in a New Era of Wearable Cardiac Devices? Comment on "Vischer et al. Comparability of a Blood-Pressure-Monitoring Smartphone Application with Conventional Measurements-A Pilot Study. Diagnostics 2022, 12, 749".

We would like to thank Drs. Hungerford and Bart for their kind comment [...].

Effect of Cuff Inflation on Blood Pressure, Arousals, Sleep Efficiency, and Desaturations: Sub-Analysis of the VAST Pilot Study.

The influence of cuff inflations on night-time measurements during 24 h ambulatory blood pressure (BP) measurements is unknown. We investigated the potential effect of cuff inflations on sleep parameters using measurements taken simultaneously with a cuffless device using pulse-transit-time (PTT). On the first day of measurement, standard cuff-based 24 h BP and cuffless measurements were simultaneously performed on the right and left arms (CUFF/PTT-D). In this experiment, 1-2 days after the first measurement, the cuffless device was worn alone (PTT-D). Only data from the cuffless device were analyzed. The following mean sleep parameters were analyzed: mean systolic and diastolic BP, arousals, sleep efficiency, total arousals, arousal per hour, and desaturations. In total, 21 individuals were prospectively enrolled. The mean (SD) age was 47 (±15) years, and 57% were female. The mean systolic asleep BP during CUFF/PTT-D and during PTT-D were 131 (±21) and 131 (±26) mmHg, respectively. The mean diastolic asleep BP values during CUFF/PTT-D and during PTT-D were 80 (±14) and 84 (±14) mmHg, respectively (p = 0.860, p = 0.100, respectively). Systolic and diastolic asleep mean difference was 0.1 (±18.0) and -3.6 (±9.8) mmHg, respectively. There were significantly more total arousals during PTT-D (p = 0.042). There were no significant differences seen in sleep efficiency (p = 0.339) or desaturations (p = 0.896) between the two measurement periods. We could not show any significant impact from cuff inflations during sleep, as documented by PTT-D measurements.

Comprehensive vasodilatation in women with acute heart failure: Novel insights from the GALACTIC randomized controlled trial.

AIMS: Sex-specific differences in acute heart failure (AHF) are both relevant and underappreciated. Therefore, it is crucial to evaluate the risk/benefit ratio and the implementation of novel AHF therapies in women and men separately. METHODS AND RESULTS: We performed a pre-defined sex-specific analysis in AHF patients randomized to a strategy of early intensive and sustained vasodilatation versus usual care in an international, multicentre, open-label, blinded endpoint trial. Inclusion criteria were AHF with increased plasma concentrations of natriuretic peptides, systolic blood pressure ≥100 mmHg, and plan for treatment in a general ward. Among 781 eligible patients, 288 (37%) were women. Women were older (median 83 vs. 76 years), had a lower body weight (median 64.5 vs. 77.6 kg) and lower estimated glomerular filtration rate (median 48 vs. 54 ml/min/1.73 m2 ). The primary endpoint, a composite of all-cause mortality or rehospitalization for AHF at 180 days, showed a significant interaction of treatment strategy and sex (p for interaction = 0.03; hazard ratio adjusted for female sex 1.62, 95% confidence interval 1.05-2.50; p = 0.03). The combined endpoint occurred in 53 women (38%) in the intervention group and in 35 (24%) in the usual care group. The implementation of rapid up-titration of renin-angiotensin-aldosterone system (RAAS) inhibitors was less successful in women versus men in the overall cohort and in patients with heart failure with reduced ejection fraction (median discharge % target dose in patients randomized to intervention: 50% in women vs. 75% in men). CONCLUSION: Rapid up-titration of RAAS inhibitors was less successfully implemented in women possibly explaining their higher rate of all-cause mortality and rehospitalization for AHF. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, unique identifier NCT00512759.

Vacuolar-type H+-ATPase-mediated proton transport in the rat parietal cell.

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.

The novel marker LTBP2 predicts all-cause and pulmonary death in patients with acute dyspnoea.

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<0.001) and non-AHF (P=0.015) patients, LTBP2 levels at presentation were significantly higher in non-survivors compared with survivors with differences on median levels being 2.2- and 1.5-fold respectively. When assessing the cause of death, LTBP2 levels were significantly higher in patients dying from pulmonary causes (P=0.0005). Overall, LTBP2 powerfully predicted early pulmonary death {AUC (area under the curve), 0.95 [95% CI (confidence interval), 0.91-0.98]}. In ROC (receiver operating characteristic) curve analyses for the prediction of 1-year mortality LTBP2 achieved an AUC of 0.77 (95% CI, 0.71-0.84); comparable with the predictive potential of NT-proBNP [N-terminal pro-B-type natriuruetic peptide; 0.77 (95% CI, 0.72-0.82)]. Importantly, the predictive potential of LTBP2 persisted in patients with AHF as the cause of dypnea (AUC 0.78) and was independent of renal dysfunction (AUC 0.77). In a multivariate Cox regression analysis, LTBP2 was the strongest independent predictor of death [HR (hazard ratio), 3.76 (95% CI, 2.13-6.64); P<0.0001]. In conclusion, plasma levels of LTBP2 present a novel and powerful predictor of all-cause mortality, and particularly pulmonary death. Cause-specific prediction of death would enable targeted prevention, e.g. with pre-emptive antibiotic therapy.

Plasma neutrophil gelatinase-associated lipocalin for the prediction of acute kidney injury in acute heart failure.

INTRODUCTION: The accurate prediction of acute kidney injury (AKI) in patients with acute heart failure (AHF) is an unmet clinical need. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel sensitive and specific marker of AKI. METHODS: A total of 207 consecutive patients presenting to the emergency department with AHF were enrolled. Plasma NGAL was measured in a blinded fashion at presentation and serially thereafter. The potential of plasma NGAL levels to predict AKI was assessed as the primary endpoint. We defined AKI according to the AKI Network classification. RESULTS: Overall 60 patients (29%) experienced AKI. These patients were more likely to suffer from pre-existing chronic cardiac or kidney disease. At presentation, creatinine (median 140 (interquartile range (IQR), 91 to 203) umol/L versus 97 (76 to 132) umol/L, P<0.01) and NGAL (114.5 (IQR, 67.1 to 201.5) ng/ml versus 74.5 (60 to 113.9) ng/ml, P<0.01) levels were significantly higher in AKI compared to non-AKI patients. The prognostic accuracy for measurements obtained at presentation, as quantified by the area under the receiver operating characteristic curve was mediocre and comparable for the two markers (creatinine 0.69; 95%CI 0.59 to 0.79 versus NGAL 0.67; 95%CI 0.57 to 0.77). Serial measurements of NGAL did not further increase the prognostic accuracy for AKI. Creatinine, but not NGAL, remained an independent predictor of AKI (hazard ratio (HR) 1.12; 95%CI 1.00 to 1.25; P=0.04) in multivariable regression analysis. CONCLUSIONS: Plasma NGAL levels do not adequately predict AKI in patients with AHF.

A model for early failure prediction of blood pressure measurement devices in a stepped validation approach.

Blood pressure monitoring (BPM) devices have to be validated according to strict international validation protocols. Each protocol requests a specific number of participants to be included. All protocols use vast amounts of resources, as three people have to be present for every measurement, making trials costly, especially when the manufacturer has no intention to execute a validation study, reflected in the low share of validated in the commercially available BPM devices. The aim of our study was to develop criteria, which could detect low accuracy devices that could not pass a validation protocol early in the course of the validation process. The 2010 European Society of Hypertension International Protocol (ESH-IP) and the Universal Standard for Validation of BPM devices (AAMI/ESH/ISO) were scrutinized for criteria which can be used for preclusion of passing. Based on this, we developed a fail model. We found that a BPM device cannot pass the ESH-IP protocol, if there are ≥27, 13, or 4 single measurements differing more than 5, 10, or 15 mmHg, respectively, from the reference. For the AAMI/ESH/ISO protocol, we developed a model, which calculates best-case standard deviations (SDs) to detect SDs which would prevent the passing of the protocol before its completion, making a stepwise validation process possible. In conclusion, we found that our model is able to predict failure of low-accuracy BPM devices early during a validation protocol if used in a stepwise-approach. This can be useful to keep costs of validation studies low and to enable investigator-initiated trials.

Prevalence and Characterisation of Severe Left Ventricular Hypertrophy Diagnosed by Echocardiography in Hypertensive Patients.

BACKGROUND: Arterial hypertension (AHT) is the leading preventable cause of death worldwide. Left ventricular hypertrophy (LVH) is one of the most important prognostic markers in hypertension and a predictor for mortality. The goals of this study were to examine the prevalence of LVH detected by echocardiography in patients with AHT and to describe patients with severe LVH. METHODS: This is a retrospective monocentric study including patients treated at a tertiary hypertension clinic. Echocardiographic data were taken from written reports from our hospital's echocardiography laboratories. We compared patients with severe LVH (septum thickness ≥ 15 mm) with patients with normal left ventricular (LV) geometry and with patients with concentric or eccentric hypertrophy regarding age, gender, comorbidities, medication, duration of hypertension, blood pressure (BP) and ECG changes at time of echocardiography. RESULTS: Twenty-nine patients (7.3%) out of four hundred patients showed severe LVH and one hundred and eighty-nine (47.3%) a normal geometry. In comparison to patients with normal geometry, patients with severe LVH were more likely to be male, older, and with more uncontrolled BP, especially regarding asleep values, multi-drug antihypertensive treatment and comorbidities. In comparison to patients with concentric or eccentric hypertrophy, patients with severe LVH had a significantly higher diastolic BP in the 24 h mean, awake and asleep values. A positive Sokolow-Lyon index did not predict LVH. However, patients with severe LVH were more likely to have T-wave-inversions V4-V6 in at least one lead. CONCLUSIONS: More than half of the patients with AHT have an abnormal geometry in our study (52.5%) and 7.3% a severe LVH. Patients with severe LVH have more often an uncontrolled AHT than patients with a normal LV geometry, despite more antihypertensive treatment. The Sokolow-Lyon index seems to be insufficient to detect LVH.

Comparability of a Blood-Pressure-Monitoring Smartphone Application with Conventional Measurements-A Pilot Study.

(1) Background: New cuffless technologies attempting blood-pressure measurements (BPM) offer possibilities to improve hypertension awareness and control. The aim of this study was to compare a smartphone application (app)-based algorithm with office BPM (OBPM). (2) Methods: We included consecutive patients with an indication for ambulatory BPM. The smartphone app (RIVA digital) acquired the pulse wave in the fingers' arterial bed using the phone's camera and estimated BP based on photoplethysmographic (PPG) waveforms. Measurements were alternatingly taken with an oscillometric cuff-based device and smartphone BPM (AppBP) on two consecutive days. AppBP were calibrated to the first OBPM. Each AppBP was compared to its CuffBP (mean of the previous/following OBPM). (3) Results: 50 participants were included, resulting in 50 AppBP values on Day 1 and 33 on Day 2 after exclusion of 225 AppBP due to insufficient quality. The mean ± SD of the differences between AppBP and CuffBP was 0.7 ± 9.4/1.0 ± 4.5 mmHg (p-value 0.739/0.201) on Day 1 and 2.6 ± 8.2/1.3 ± 4.1 mmHg (p-value 0.106/0.091) on Day 2 for systolic/diastolic values, respectively. There were no significant differences between the deviations on Day 1 and Day 2 (p-value 0.297/0.533 for systolic/diastolic values). Overall, there were 10 (12%) systolic measurement pairs differing by >15 mmHg. (4) Conclusions: In this pilot evaluation, the RIVA Digital app shows promising results when compared to oscillometric cuff-based measurements, especially regarding diastolic values. Its differences between AppBP−CuffBP have a good stability one day after calibration. Before clinical use, signal acquisition needs improvement and the algorithm needs to undergo formal validation against a gold-standard BPM method.

Zinc salts provide a novel, prolonged and rapid inhibition of gastric acid secretion.

OBJECTIVES: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: Our findings demonstrate that zinc offers a novel rapid and prolonged therapy to inhibit gastric acid secretion in human and rat models.

Direct comparison of serial B-type natriuretic peptide and NT-proBNP levels for prediction of short- and long-term outcome in acute decompensated heart failure.

INTRODUCTION: Monitoring treatment efficacy and assessing outcome by serial measurements of natriuretic peptides in acute decompensated heart failure (ADHF) patients may help to improve outcome. METHODS: This was a prospective multi-center study of 171 consecutive patients (mean age 80 73-85 years) presenting to the emergency department with ADHF. Measurement of BNP and NT-proBNP was performed at presentation, 24 hours, 48 hours and at discharge. The primary endpoint was one-year all-cause mortality; secondary endpoints were 30-days all-cause mortality and one-year heart failure (HF) readmission. RESULTS: During one-year follow-up, a total of 60 (35%) patients died. BNP and NT-proBNP levels were higher in non-survivors at all time points (all P < 0.001). In survivors, treatment reduced BNP and NT-proBNP levels by more than 50% (P < 0.001), while in non-survivors treatment did not lower BNP and NT-proBNP levels. The area under the ROC curve (AUC) for the prediction of one-year mortality increased during the course of hospitalization for BNP (AUC presentation: 0.67; AUC 24 h: 0.77; AUC 48 h: 0.78; AUC discharge: 0.78) and NT-proBNP (AUC presentation: 0.67; AUC 24 h: 0.73; AUC 48 h: 0.75; AUC discharge: 0.77). In multivariate analysis, BNP at 24 h (1.02 [1.01-1.04], P = 0.003), 48 h (1.04 [1.02-1.06], P < 0.001) and discharge (1.02 [1.01-1.03], P < 0.001) independently predicted one-year mortality, while only pre-discharge NT-proBNP was predictive (1.07 [1.01-1.13], P = 0.016). Comparable results could be obtained for the secondary endpoint 30-days mortality but not for one-year HF readmissions. CONCLUSIONS: BNP and NT-proBNP reliably predict one-year mortality in patients with ADHF. Prognostic accuracy of both biomarker increases during the course of hospitalization. In survivors BNP levels decline more rapidly than NT-proBNP levels and thus seem to allow earlier assessment of treatment efficacy. Ability to predict one-year HF readmission was poor for BNP and NT-proBNP. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00514384.

How should we measure blood pressure? Implications of the fourth blood pressure measurement in office blood pressure.

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 < .0005 for all). In participants with an S1S2 (n = 206) and D1D2 (n = 60) difference >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).

Improved agreement and diagnostic accuracy of a cuffless 24-h blood pressure measurement device in clinical practice.

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 < 0.001). TestBP-V1.5 area under the curve (95% confidence interval) versus RefBP for hypertension detection was 0.92 (0.86; 0.99), 0.94 (0.88; 0.99) and 0.77 (0.66; 0.88) for systolic and 0.92 (0.86; 0.99), 0.92 (0.85; 0.99) and 0.84 (0.74; 0.94) for diastolic 24 h, awake and asleep BP respectively. TestBP-V1.5 detected elevated systolic/diastolic mean 24 h-BP with a 95%/90% sensitivity and 65%/70% specificity. Highest Youden's Index was systolic 133 (sensitivity 95%/specificity 80%) and diastolic 87 mmHg (sensitivity 81%/specificity 98%). The update improved the agreement to RefBP. TestBP was excellent for detecting 24 h and awake hypertensive BP values but not for asleep BP values.

Accuracy of abbreviated protocols for unattended automated office blood pressure measurements, a retrospective study.

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.

Hemodynamic profiles in treatment-naive arterial hypertension and their clinical implication for treatment choice: an exploratory post hoc analysis.

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.

Use of myeloperoxidase for risk stratification in acute heart failure.

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 (< or = 99 vs >99 pmol/L) and BNP (median of < or = 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.