Hypertensive emergencies and urgencies: a preliminary report of the ongoing Italian multicentric study ERIDANO.

Hypertensive urgencies (HU) and hypertensive emergencies (HE) are challenges for the Emergency Department (ED). A prospective multicentre study is ongoing to characterize patients with acute hypertensive disorders, prevalence of subclinical hypertension-mediated organ damage (HMOD), short- and long-term prognosis; this is a preliminary report. Patients admitted to the ED with symptomatic blood pressure (BP) ≥180/110 mmHg were enrolled. They were managed by ED personnel according to their clinical presentations. Subsequently they underwent clinical evaluation and subclinical HMOD assessment at a Hypertension Centre within 72 h from enrolment. 122 patients were included in this report. Mean age was 60.7±13.9 years, 52.5% were females. 18 (14.8%) patients were diagnosed with HE, 108 (88.5%) with HU. There were no differences in gender, BMI, and cardiovascular comorbidities between groups. At ED discharge, 66.7% and 93.6% (p = 0.003) of HE and HU patients, respectively, had BP < 180/110 mmHg. After 72 h, 34.4% of patients resulted normotensive; 35.2%, 22.1%, and 8.2% had hypertension grade 1, 2, and 3, respectively. Patients with uncontrolled BP at office evaluation had higher vascular HMOD (49.1 vs. 25.9%, p = 0.045). Cardiac (60 vs. 34%, p = 0.049), renal (27.8 vs. 9.6%, p = 0.010) and cerebral (100 vs. 21%, p < 0.001) HMOD was more frequent in HE compared to HU group. HE showed greater cardiac, renal, and cerebral subclinical HMOD, compared to HU. 72-hours BP control is not associated with different HMOD, except for vascular HMOD; therefore, proper comprehensive examination after discharge from the ED could provide added value in cardiovascular risk stratification of such patients. One third of patients with acute blood pressure rise evaluated to the ED resulted normotensive at office evaluation (<72 hours after discharge). Patients with hypertensive emergency showed greater cardiac, renal, and cerebral subclinical HMOD, compared to the patients with hypertensive urgency. BP: blood pressure; HMOD: hypertension-mediated organ damage; y.o.: years old; mo.: months.

Patients with Very High Risk of Cardiovascular Adverse Events during Carfilzomib Therapy: Prevention and Management of Events in a Single Center Experience.

Carfilzomib (CFZ) improves the prognosis of multiple myeloma (MM) patients but has shown cardiovascular toxicity. The risk stratification of cardiovascular adverse events (CVAEs) now seems well established, while little is known about the course and management of patients with a high-cardiovascular-risk profile or experiencing CVAEs during therapy. Therefore, we aimed to describe our experience in decision making to support health professionals in selecting the best management strategies to prevent and treat CVAEs. A total of 194 patients with indication to CFZ underwent baseline evaluation of CVAEs risk and were prospectively followed. We propose a novel approach, which includes advanced cardiac imaging testing for patients at high baseline CV risk to rule out clinical conditions that could contraindicate starting CFZ. After baseline evaluation, 19 (9.8%) patients were found at high risk of CVAEs: 13 (6.7%) patients underwent advanced cardiac testing and 3 (1.5%) could not receive CFZ due to CV contraindications. A total of 178 (91.7%) patients started CFZ: 82 (46%) experienced arterial-hypertension-related events and 37 (20.8%) major CVAEs; 19 (10.7%) patients had to discontinue or modify the CFZ dosing regimen. Along with baseline risk stratification, subsequent cardiovascular clinical events and diagnostic follow-up both provided critical data to help identify conditions that could contraindicate the anticancer therapy.

Carfilzomib-Based Regimen and Cardiotoxicity in Multiple Myeloma: Incidence of Cardiovascular Events and Organ Damage in Carfilzomib-Dexamethasone versus Carfilzomib-Lenalidomide-Dexamethasone. A Real-Life Prospective Study.

Carfilzomib-mediated cardiotoxicity in multiple myeloma (MM) is a well-established adverse effect, however limited data are available on the comparison of cardiovascular complications in patients treated with Carfilzomib-dexamethasone (target dose of K 56 mg/m2) versus Carfilzomib-lenalidomide-dexamethasone (target dose of K 27 mg/m2) beyond controlled trials. A total of 109 patients were enrolled, 47 (43%) received Kd and 62 (57%) KRd. They then underwent a baseline and follow-up evaluation including trans-thoracic echocardiography and arterial stiffness estimation. All types of cardiovascular and hypertensive events occurred more frequently in the Kd group compared with the KRd (59% vs. 40% and 55% vs. 35.5% patients, respectively, p ≤ 0.05), with higher incidence of hypertensive. The time of onset of any type of CVAE, and of major and hypertensive events was shorter in the Kd regimen (p ≤ 0.05). At follow-up, Kd patients more frequently developed signs of cardiac (decline of global longitudinal strain) and vascular organ damage (rise of pulse wave velocity), as compared with KRd. Despite the older age, longer history of MM and longer period of pre-treatment of Kd patients, these factors did not increase the probability of incidence for all types of cardiovascular events at multivariate analysis (p > 0.05). In conclusion, the Kd regimen showed greater cardiovascular toxicity and earlier onset of events with respect to KRd. Thus, a closer and thorough follow-up should be considered.

Cardiovascular Hypertension-Mediated Organ Damage in Hypertensive Urgencies and Hypertensive Outpatients.

Background: The prevalence of hypertension mediated organ damage (HMOD) in patients attending the Emergency Department (ED) with symptomatic blood pressure (BP) rise is unknown, and whether HMOD varies between asymptomatic and symptomatic patients with grade 3 hypertension is unclear. Aim: This study aimed to investigate cardiac and vascular HMOD in hypertensive urgencies (HU) and asymptomatic outpatients with grade 1-3 hypertension. Methods: Patients attending the ED with a symptomatic BP rise ≥180/110 mmHg were prospectively enrolled (HU group), after the exclusion of acute organ damage. HMOD and BP were assessed after 72 h from ED discharge in an office setting. These patients were matched by age and sex to outpatients with grade 3 hypertension (Grade 3 group), and by age, sex, and 72 h office BP values to outpatients with any grade hypertension (Control group). Results: A total of 304 patients were enrolled (76 patients in the HU group, 76 in the Grade 3 group, and 152 in the Control group). Grade 3 patients had increased left ventricular mass (LVMi) compared to patients with HU (106.9 ± 31.5 vs. 96.1 ± 30.7 g/m2, p = 0.035). Severe left ventricular hypertrophy (LVH) was more frequent in grade 3 (21.1 vs. 5.3%, p = 0.004), and pulse wave velocity (PWV) was similar in the two groups. There was no difference in LVMi between ED and Control patients (96.1 ± 30.7 vs. 95.2 ± 26.6 g/m2, p = 0.807). LVH prevalence was similar (43.4 vs. 35.5%, p = 0.209, respectively), but patients with HU had thicker interventricular septum (11.9 ± 2.2 vs. 11.1 ± 2.2 mm, p = 0.007). PWV was similar between these two groups. Patients with HU needed more antihypertensive drugs than Control patients (2 vs. 1, p < 0.001). Conclusions: Patients with HU had a better cardiac HMOD profile than outpatients with grade 3 hypertension. Their cardiac and vascular HMOD is more comparable to an outpatient with similar in-office BP, although they need more antihypertensive medications.

LAMP-5 is an essential inflammatory-signaling regulator and novel immunotherapy target for mixed lineage leukemia-rearranged acute leukemia.

Although great advances have been made in understanding the pathobiology of mixed lineage leukemia-rearranged (MLL-r) leukemias, therapies for this leukemia have remained limited, and clinical outcomes remain bleak. In order to identify novel targets for immunotherapy treatments, we compiled a lineage-independent MLL-r leukemia gene signature using publicly available data sets. Data from large leukemia repositories were filtered through the in silico human surfaceome, providing a list of highly predicted cell surface proteins overexpressed in MLL-r leukemias. LAMP5, a lysosomal associated membrane protein, is expressed highly and specifically in MLL-r leukemia. We found that LAMP5 is a direct target of the oncogenic MLL-fusion protein. LAMP5 depletion significantly inhibited leukemia cell growth in vitro and in vivo. Functional studies showed that LAMP-5 is a novel modulator of innate-immune pathways in MLL-r leukemias. Downregulation of LAMP5 led to inhibition of NF-kB signaling and increased activation of type-1 interferon signaling downstream of Toll-like receptor/interleukin 1 receptor activation. These effects were attributable to the critical role of LAMP-5 in transferring the signal flux from interferon signaling endosomes to pro-inflammatory signaling endosomes. Depletion of IRF7 was able to partially rescue the cell growth inhibition upon LAMP5 downregulation. Lastly, LAMP-5 was readily detected on the surface of MLL-r leukemia cells. Targeting surface LAMP-5 using an antibody-drug conjugate leads to significant cell viability decrease specifically in MLL-r leukemias. Overall, based on the limited expression throughout human tissues, we postulate that LAMP-5 could potentially serve as an immunotherapeutic target with a wide therapeutic window to treat MLL-r leukemias.

A Novel Approach to Left Ventricular Filling Pressure Assessment: The Role of Hemodynamic Forces Analysis.

Background: Diastolic function in patients with heart failure is usually impaired, resulting in increased left ventricular (LV) filling pressures, whose gold standard assessment is right heart catheterization (RHC). Hemodynamic force (HDF) analysis is a novel echocardiographic tool, providing an original approach to cardiac function assessment through the speckle-tracking technology. The aim of our study was to evaluate the use of HDFs, both alone and included in a new predictive model, as a potential novel diagnostic tool of the diastolic function. Methods: HDF analysis was retrospectively performed in 67 patients enrolled in the "Right1 study." All patients underwent RHC and echocardiography up to 2 h apart. Increased LV filling pressure (ILFP) was defined as pulmonary capillary wedge pressure (PCWP) ≥ 15 mmHg. Results: Out of 67 patients, 33 (49.2%) showed ILFP at RHC. Diastolic longitudinal force (DLF), the mean amplitude of longitudinal forces during diastole, was associated with the presence of ILFP (OR = 0.84 [0.70; 0.99], p = 0.046). The PCWP prediction score we built including DLF, ejection fraction, left atrial enlargement, and e' septal showed an AUC of 0.83 [0.76-0.89], with an optimal internal validation. When applied to our population, the score showed a sensitivity of 72.7% and a specificity of 85.3%, which became 66.7 and 94.4%, respectively, when applied to patients classified with "indeterminate diastolic function" according to the current recommendations. Conclusion: HDF analysis could be an additional useful tool in diastolic function assessment. A scoring system including HDFs might improve echocardiographic accuracy in estimating LV filling pressures. Further carefully designed studies could be useful to clarify the additional value of this new technology.

Accuracy of a new instrument for noninvasive evaluation of pulse wave velocity: the Arterial sTiffness faitHful tOol aSsessment project.

BACKGROUND: Large artery stiffness, assessed by carotid--femoral pulse wave velocity (cfPWV), is a major risk factor for cardiovascular events, commonly used for risk stratification. Currently, the reference device for noninvasive cfPWV is SphygmoCor but its cost and technically challenging use limit its diffusion in clinical practice. AIM: To validate a new device for noninvasive assessment of cfPWV, ATHOS (Arterial sTiffness faitHful tOol aSsessment), designed in collaboration with the Politecnico di Torino, against the reference noninvasive method represented by SphygmoCor. METHODS: Ninety healthy volunteers were recruited. In each volunteer, we assessed cfPWV, using SphygmoCor (PWVSphygmoCor) and ATHOS (PWVATHOS) devices in an alternate fashion, following the ARTERY Society guidelines. The accuracy was assessed by Bland--Altman plot, and reproducibility was assessed by interoperator correlation coefficient (ICC). RESULTS: Mean PWVATHOS and mean PWVSphygmoCor were 7.88 ±â€Š1.96 and 7.72 ±â€Š1.95 m/s, respectively. Mean difference between devices was 0.15 ±â€Š0.56 m/s, with a high correlation between measurements (r = 0.959, P < 0.001). Considering only PWV values at least 8 m/s (n = 30), mean difference was 0.1 ±â€Š0.63 m/s. The ICC was 97.7% with ATHOS. CONCLUSION: ATHOS showed an excellent level of agreement with SphygmoCor, even at high PWV values, with a good reproducibility. Its simplicity of use could help increase clinical application of PWV assessment, improving patients' cardiovascular risk stratification.

Effects of Carfilzomib Therapy on Left Ventricular Function in Multiple Myeloma Patients.

Background: Carfilzomib improves the prognosis of multiple myeloma (MM) patients but significantly increases cardiovascular toxicity. The timing and effect of Carfilzomib therapy on the left ventricular function is still under investigation. We sought to assess the echocardiographic systo-diastolic changes, including global longitudinal strain (GLS), in patients treated with Carfilzomib and to identify predictors of increased risk of cardiovascular adverse events (CVAEs) during therapy. Methods: Eighty-eight patients with MM performed a baseline cardiovascular evaluation comprehensive of transthoracic echocardiogram (TTE) before the start of Carfilzomib therapy and after 6 months. All patients were clinically followed up to early identify the occurrence of CVAEs during the whole therapy duration. Results: After Carfilzomib treatment, mean GLS slightly decreased (-22.2% ± 2.6 vs. -21.3% ± 2.5; p < 0.001). Fifty-eight percent of patients experienced CVAEs during therapy: 71% of them had uncontrolled hypertension, and 29% had major CVAEs or CV events not related to arterial hypertension. GLS variation during therapy was not related to an increased risk of CVAEs; however, patients with baseline GLS ≥ -21% and/or left ventricular ejection fraction (LVEF) ≤ 60% had a greater risk of major CVAEs (OR = 6.2, p = 0.004; OR = 3.7, p = 0.04, respectively). Carfilzomib led to a higher risk of diastolic dysfunction (5.6 vs. 13.4%, p = 0.04) and to a rise in E/e' ratio (8.9 ± 2.7 vs. 9.7 ± 3.7; p = 0.006). Conclusion: Carfilzomib leads to early LV function impairment early demonstrated by GLS changes and diastolic dysfunction. Baseline echocardiographic parameters, especially GLS and LVEF, might improve cardiovascular risk stratification before treatment.

Multiple Myeloma Patients Undergoing Carfilzomib: Development and Validation of a Risk Score for Cardiovascular Adverse Events Prediction.

Cardiovascular adverse events (CVAEs) are linked to Carfilzomib (CFZ) therapy in multiple myeloma (MM); however, no validated protocols on cardiovascular risk assessment are available. In this prospective study, the effectiveness of the European Myeloma Network protocol (EMN) in cardiovascular risk assessment was investigated, identifying major predictors of CVAEs. From January 2015 to March 2020, 116 MM patients who had indication for CFZ therapy underwent a baseline evaluation (including blood pressure measurements, echocardiography and arterial stiffness estimation) and were prospectively followed. The median age was 64.53 ± 8.42 years old, 56% male. Five baseline independent predictors of CVAEs were identified: office systolic blood pressure, 24-h blood pressure variability, left ventricular hypertrophy, pulse wave velocity value and global longitudinal strain. The resulting 'CVAEs risk score' distinguished a low- and a high-risk group, obtaining a negative predicting value for the high-risk group of 90%. 52 patients (44.9%) experienced one or more CVAEs: 17 (14.7%) had major and 45 (38.7%) had hypertension-related events. In conclusion, CVAEs are frequent and a specific management protocol is crucial. The EMN protocol and the risk score proved to be useful to estimate the baseline risk for CVAEs during CFZ therapy, allowing the identification of higher-risk patients.

Central pulse pressure is inversely associated with proximal aortic remodelling.

OBJECTIVES: Hypertension leads to aortic stiffening and dilatation but unexpected data from the Framingham Heart Study showed an inverse relationship between brachial pulse pressure and aortic diameter. Aortic dilatation would not only lead to lower pulse pressure but also to a worse prognosis (cardiac events, heart failure). Invasive pressure may be more informative but data are lacking. AIM: This study evaluated the relationship between invasively measured central blood pressure and proximal aortic diameter. METHODS: In 71 consecutive patients referred to invasive haemodynamic study, proximal aortic remodelling was evaluated in terms of Z-score, comparing diameters measured at the sinus of Valsalva to the diameter expected according to patients' age, sex and body height. Pressures were recorded directly in the proximal aorta by means of a catheter before coronary assessment. RESULTS: The mean invasive aortic SBPs and DBPs were 146 ±â€Š23 and 78 ±â€Š13 mmHg, respectively, giving a central pulse pressure (cPP inv) of 68 ±â€Š21 mmHg. Proximal aortic diameter was 34.9 ±â€Š19.4 mm, whereas Z-score was -0.3 ±â€Š1.7. Patients with higher cPPinv showed a significantly lower Z-score (-0.789 vs. 0.155, P = 0.001). cPPinv was inversely related to Z-score (R = -0.271, P = 0.022) independently from age, mean blood pressure and heart rate (ß = -0.241, P = 0.011). CONCLUSION: Aortic root Z-score is inversely associated with invasively measured central pulse pressure in a cohort of patients undergoing invasive coronary assessment. Remodelling at the sinuses of Valsalva may be a compensatory mechanism to limit pulse pressure.

Prognostic role of the ascending aorta dilatation in patients with arterial hypertension.

BACKGROUND: Ascending aorta (ASC) dilatation (AAD) is a common finding in arterial hypertension, affecting about 15% of hypertensive patients. AAD is associated with an increase in cardiac and vascular hypertension-related organ damage, but its prognostic role is unknown. The aim of the study was to evaluate the prognostic value of AAD as predictor of cardiovascular events in essential hypertensive patients. METHODS: Recruited patients underwent two-dimensional transthoracic echocardiography from 2007 to 2013 and followed-up for cardiovascular events until November 2018 by phone call and hospital information system check. ASC diameter and AAD were defined using both absolute and scaled definitions. Four hundred and twenty-three hypertensive patients were included in our study. RESULTS: During a median follow-up of 7.4 years (interquartile range 5.6-9.1 years), 52 events were observed. After adjusting for age, sex and BSA, both ASC diameter and AAD definition, according to ARGO-SIIA project, resulted associated with a greater risk of cardiovascular event (both P < 0.010), even after adjusting for major confounders (both P < 0.010). Moreover, we observed that the assessment of ASC improves risk stratification compared with pulse wave velocity alone, and that in absence of AAD, sinus of valsalva dilatation lost any prognostic value (P = 0.262). CONCLUSIONS: ASC diameter and AAD are both associated with a greater risk of cardiovascular events. ASC should be assessed to optimize risk stratification in hypertensive patients and its dilatation may be considered as a surrogate for vascular organ damage.

A New Noninvasive System for Clinical Pulse Wave Velocity Assessment: The Athos Device.

This paper presents a low cost, noninvasive, clinical-grade Pulse Wave Velocity evaluation device. The proposed system relies on a simultaneous acquisition of femoral and carotid pulse waves to improve estimation accuracy and correctness. The sensors used are two high precision MEMS force sensors, encapsulated in two ergonomic probes, and connected to the main unit. Data are then wirelessly transmitted to a standard laptop, where a dedicated graphical user interface (GUI) runs for analysis and recording. Besides the interface, the Athos system provides a Matlab algorithm to process the signals quickly and achieve a reliable PWV assessment. To better compare the results at the end of each analysis, a detailed report is generated, including all the relevant examination information (subject data, mean PTT, and obtained PWV). A pre-clinical study was conducted to validate the system by realizing several Pulse Wave Velocity measurements on ten heterogeneous healthy subjects of different ages. The collected results were then compared with those measured by a well-established and largely more expensive clinical device (SphygmoCor).

Lung Ultrasonography for the Diagnosis of SARS-CoV-2 Pneumonia in the Emergency Department.

STUDY OBJECTIVE: Accurate diagnostic testing to identify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is critical. Although highly specific, SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) has been shown in clinical practice to be affected by a noninsignificant proportion of false-negative results. This study seeks to explore whether the integration of lung ultrasonography with clinical evaluation is associated with increased sensitivity for the diagnosis of coronavirus disease 2019 pneumonia, and therefore may facilitate the identification of false-negative SARS-CoV-2 RT-PCR results. METHODS: This prospective cohort study enrolled consecutive adult patients with symptoms potentially related to SARS-CoV-2 infection who were admitted to the emergency department (ED) of an Italian academic hospital. Immediately after the initial assessment, a lung ultrasonographic evaluation was performed and the likelihood of SARS-CoV-2 infection, based on both clinical and lung ultrasonographic findings ("integrated" assessment), was recorded. RT-PCR SARS-CoV-2 detection was subsequently performed. RESULTS: We enrolled 228 patients; 107 (46.9%) had SARS-CoV-2 infection. Sensitivity and negative predictive value of the clinical-lung ultrasonographic integrated assessment were higher than first RT-PCR result (94.4% [95% confidence interval {CI} 88.2% to 97.9%] versus 80.4% [95% CI 71.6% to 87.4%] and 95% [95% CI 89.5% to 98.2%] versus 85.2% [95% CI 78.3% to 90.6%], respectively). Among the 142 patients who initially had negative RT-PCR results, 21 tested positive at a subsequent molecular test performed within 72 hours. All these false-negative cases were correctly identified by the integrated assessment. CONCLUSION: This study suggests that, in patients presenting to the ED with symptoms commonly associated with SARS-CoV-2 infection, the integration of lung ultrasonography with clinical evaluation has high sensitivity and specificity for coronavirus disease 2019 pneumonia and it may help to identify false-negative results occurring with RT-PCR.

Local transversal aortic strain is impaired in ascending aorta dilatation.

BACKGROUND: Ascending aorta dilatation is found in 13% of hypertensive patients. Little is known about elastic properties of ascending aorta in such patients. Echo-based transverse aortic strain analysis can describe mechanical properties of ascending aorta but has never been applied to patients with ascending aorta dilatation. AIM: To assess mechanical properties of ascending aorta by transverse aortic strain analysis (as ß2-stiffness index) in hypertensive patients with ascending aorta dilatation and association between mechanical properties of ascending aorta and cardiovascular damage. METHODS: A total of 100 hypertensive outpatients underwent transthoracic echocardiography and assessment of pulse wave velocity (PWV). Strain analysis of ascending aorta was performed with echocardiographic speckle-tracking software. Patients were divided in three groups based on ascending aorta diameter: less than 40, 40-45, and at least 45 mm. RESULTS: Beta-SI increased exponentially with ascending aorta dimensions (P < 0.001). Patients with ascending aorta dilatation had Beta-SI significantly higher than those with normal ascending aorta diameter. A greater proportion of patient with impaired (i.e., elevated) Beta-SI was present in groups with larger ascending aorta (18.2 vs. 48.4 vs. 80%, respectively, P < 0.05). On multivariate logistic regression only impaired Beta-SI predicted ascending aorta dilatation (P < 0.001). Beta-SI was related to cardiovascular damage in terms of left ventricular (LV) mass (LV mass indexed to BSA, P = 0.030) and PWV (P = 0.028). Patients with high Beta-SI had greater LV mass indexed to BSA (117 ±â€Š47 vs. 94 ±â€Š24 g/m2; P = 0.010) and PWV (10.20 ±â€Š2.99 vs. 8.63 ±â€Š1.88 m/s; P = 0.013). CONCLUSION: Ascending aorta dilatation is associated with increased local aortic stiffness in hypertensive patients. Strain analysis adds functional information to the mere morphological evaluation of aortic diameter and could be a useful tool to better define cardiovascular risk in this population.

Accuracy of a Symptom-Based Approach to Identify Hypertensive Emergencies in the Emergency Department.

BACKGROUND: A hierarchical symptoms-based diagnostic strategy relying on the presence of five main symptoms (chest pain, acute dyspnea, neurological symptoms, headache, visual impairment) was recently proposed to diagnose patients with hypertensive emergency. However, poor scientific evidence is available about the role of symptoms in both diagnosis and management of acute hypertensive disorders. METHODS: Data from 718 patients presenting to the emergency department of the "Città della Salute e della Scienza" Hospital of Turin with systolic blood pressure > 180 and/or diastolic blood pressure > 110 mm/Hg were retrospectively analyzed. The accuracy of the typical symptoms for identification of hypertensive emergencies was assessed. RESULTS: A total of 79 (11%) out of 718 patients were diagnosed with hypertensive emergencies (51% had cardiovascular and 49% neurovascular acute organ damage). Patients with hypertensive emergencies were older and with higher prevalence of coronary artery disease and chronic heart failure than patients with uncontrolled hypertension. Typical symptoms could discriminate true hypertensive emergency from uncontrolled hypertension with 64% accuracy, 94% sensitivity, and 60% specificity. CONCLUSION: Typical symptoms might be used as a simple screening test (99% negative predictive value) in the emergency department to select for further evaluations of patients with suspected hypertensive emergencies among those with acute hypertensive disorders.

Correction: Dependency on the TYK2/STAT1/MCL1 axis in anaplastic large cell lymphoma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Pulse wave velocity and short-term outcome in patients requiring intravascular volume expansion: a pilot study.

BACKGROUND: Fluid therapy has a pivotal role in the management of acutely ill patients. However, whether or not a patient can tolerate additional intravascular volume is controversial and optimal strategy is unknown. Carotid femoral pulse wave velocity (cfPWV) evaluates arterial stiffness. OBJECTIVE: To determine whether cfPWV can predict the ability of patients to tolerate clinically indicated acute fluid expansion. METHODS: 50 consecutive patients requiring intravascular volume expansion were prospectively recruited in intensive care units. All subjects underwent transthoracic echocardiography, pulmonary ultrasound assessment, and a cfPWV study (S. Giovanni Bosco Hospital in Turin, Italy, between 2015 and 2016) at baseline and after 24 hours. Acute outcomes were registered at 24 hours ("soft" end points) and 30 days ('hard' end points: death, acute myocardial infarction, stroke, occurrence of atrial fibrillation, need for dialysis) after initial fluid therapy. Multivariate logistic regression was used to assess association of the initial cfPWV with outcomes. RESULTS: cfPWV was significantly higher (10.6±3.6 vs 7.4±2.2 m/s, P<0.0001) in subjects who met the prespecified combined endpoints (hard or soft) than in those who did not. After adjustment for confounding factors, initial cfPWV was significantly and independently associated with the occurrence of hard events (OR=2.8 (95% CI 1.36 to 5.97), P=0.005; area under the receiver operating characteristic curve 84%). cfPWV of <9 m/s had a negative predictive value of 93%, excluding hard events associated with fluid expansion. CONCLUSION: cfPWV appears to reflect the ability of the patient to tolerate an intravascular fluid expansion when clinically indicated. Increased cfPWV could help to identify subjects at greater risk of developing signs and symptoms of fluid overload.

Proximal aortic diameter evolution in hypertensive patients with mild-to-moderate aortic dilatation: a 5-year follow-up experience.

BACKGROUND: Aortic dilatation is common in hypertensive patients and is associated with higher risk of cardiovascular events. Parameters predicting further dilatation during lifetime are poorly understood. AIM: To predict the midterm aortic diameter evolution in a cohort of hypertensive patients with known aortic dilatation at Sinus of Valsalva (SOV) level. METHODS: We prospectively analyzed a cohort of essential hypertensive outpatients without any other known risk factor for aortic dilatation. They underwent serial echocardiographic evaluations from 2003 to 2016. RESULTS: Two hundred and forty-two hypertensive outpatients with a mild-to-moderate (37-53 mm) aortic dilatation were followed up for at least 5 years. Mean growth rate was 0.08 ±â€Š0.35 mm/year. No clinical or anthropometric parameters were significantly different in patients with and without aortic diameter increase. Aortic z score (number of standard deviations from the average value observed in the general population) at baseline was inversely associated with growth rate (R 0.04, P < 0.05). Aortic diameter at first visit, demographic and echocardiographic variables were major determinants of aortic diameter at second visit, accounting for about 90% of its total variability. CONCLUSION: Mean growth rate of proximal aorta in hypertensive patients with known aortic dilatation was of about 0.1 mm/year. Dilatation over time is slower in patients with increased rather than normal aortic z score. Eventually, it could be possible to reliably predict aortic diameter at few months from first visit.

Current assessment of pulse wave velocity: comprehensive review of validation studies.

OBJECTIVE: Carotid-femoral pulse wave velocity (PWV) is considered the gold standard for arterial stiffness assessment in clinical practice. A large number of devices to measure PWV have been developed and validated. We reviewed different validation studies of PWV estimation techniques and assessed their conformity to the Artery Society Guidelines and the American Heart Association recommendations. METHODS: Pubmed and Medline (1995-2017) were searched to identify PWV validation studies. Of the 96 article retrieved, 26 met the inclusion criteria. RESULTS: Several devices had been developed and validated to noninvasively measure arterial stiffness, using applanation tonometry (SphygmoCor, PulsePen), piezoelectric mechanotransducers (Complior), cuff-based oscillometry (Arteriograph, Vicorder and Mobil-O-Graph), photodiode sensors (pOpmètre) and devices assessing brachial-ankle pulse wave velocity and cardiac-ankle PWV. Ultrasound technique and MRI remain confined to clinical research. Good agreement was found with the Artery Society Guidelines. Two studies (Complior, SphygmoCor Xcel) showed best adherence with the guidelines. In Arteriograph, MRI, ultrasound and SphygmoCor Xcel validation studies sample size was smaller than the minimum suggested by the guidelines. High discrepancies between devices were shown in distance estimation: in two studies (Arteriograph, Complior) path length was estimated in conformity to the guidelines. Transit time was calculated using the intersecting tangent method, but in two studies (Vicorder, pOpmètre) best agreement was found using the maximum of the second derivative. Six studies reached the accuracy level 'excellent' defined in the Artery guidelines. CONCLUSION: Method to assess transit time and path length need validation in larger populations. Further studies are required in different risk population to implement clinical applicability of every device.