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Blood pressure (BP) variability (BPV) is an independent predictor of cardiovascular (CV) events. The role of BPV in defining risk of cancer therapy-related cardiovascular toxicity (CTR-CVT) is currently unknown. The aims of this study were: (i) to evaluate BPV in a population of patients with Multiple Myeloma, undergoing proteasome inhibitors therapy; (ii) to assess the predictive value of BPV for CTR-CVT; (iii) to analyze clusters of subjects based on BPV. One hundred twenty-four patients underwent a baseline evaluation, including Ambulatory Blood Pressure Monitoring (ABPM), PWV, and Echocardiography. BPV was assessed through ABPM-based standard deviation (SD), weighted standard deviation (wSD), coefficient of variation (CoV), average real variability (ARV), and variability independent of the mean (VIM). Individuals who developed CTR-CVT had a higher baseline BPV. Furthermore, night-time BPV was associated with CTR-CVT, independently of age, smoking, BP, diabetes, dyslipidemia, and kidney function (night-time systolic CoV: adjusted OR 1.09 [1.01-1.21]; night-time systolic VIM: adjusted OR 1.18 [1.01-1.39]). Cut-offs for these BPV parameters were identified as predictors of CTR-CVT occurrence: 10.5 for night-time systolic CoV; 7.8 and 6.4 for systolic and diastolic night-time VIM. Clustering analysis identified subgroups of subjects characterized by the highest BPV, who had a greater prevalence of events, but no differences in other CV risk determinants. Short-term BPV is an independent predictor of CTR-CVT. BPV may enhance the precision of risk stratification in cancer patients, enabling identification of individuals at higher risk who would not be recognized, if traditional prognostic indicators were the sole applied criteria. On the left panel in the figure, the distribution of blood pressure variability (BPV) in the population according to cancer therapy-related cardiovascular toxicity occurrence; in the central panel, association of blood pressure variability with events and cutoffs values; in the right panel, clustering analysis results based on BPV levels. Histogram and radar plot represent events and BPV indexes distribution in the three clusters, respectively. ARV, average real variability; BPV, Blood Pressure Variability; CTR-CVT, cancer therapy-related cardiovascular toxicity; CoV, coefficient of variation; DBP, Diastolic blood pressure; SBP, Systolic blood pressure; SD, standard deviation; VIM, variability independent of the mean; wSD, weighted standard deviation., Competing Interests: Compliance with ethical standards. Conflict of interest: Alberto Milan received honoraria for advisory board from Amgen. Sara Bringhen received honoraria from Bristol-Myers Squibb, Celgene, Amgen, and Janssen; advisory boards for Amgen, Karyopharm, Janssen, and Celgene; consultancy fees from Takeda and Janssen. Francesca Gay received honoraria from Amgen, Janseen, Celgene, BMS, Takeda, and Abbvie; advisory boards for Amgen, Janseen, Celgene, BMS, Takeda, and Abbvie; advisory adaptive for Roche Oncopeptides. The other authors declare no conflict of interest. The other authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, and/or interpretation of data; in the writing of the manuscript and/or in the decision to publish the results., (© 2025. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: Heart failure with preserved ejection fraction (HFpEF) is a high prevalence condition, with high rates of hospitalization and mortality. Arterial hypertension is the main risk factor for HFpEF. Among hypertensive patients, alterations in cardiac and vascular morphology identify hypertension-mediated organ damage (HMOD). Cardiac HMOD in terms of ventricular hypertrophy and diastolic dysfunction is a continuum between the preclinical condition (arterial hypertension) and HFpEF. In hypertensive patients, it is currently unknown what is the prevalence of individuals classifiable as being at high risk of developing HFpEF and whether aortic morphofunctional vascular changes are present., Aim: This study seeks to retrospectively assess the prevalence of echocardiographic alterations consistent with the diagnosis of HFpEF in a cohort of patients with essential arterial hypertension, and the prevalence of vascular HMOD (V-HMOD) in different risk categories of patients., Methods: Hypertensive outpatients referred at the Hypertension Center of Turin from 2003 to 2021 were retrospectively evaluated. Patients with a previous diagnosis of heart failure and known cardiovascular events were excluded. A predictive model associated with the risk of HFpEF development was calculated using echocardiographic variables. V-HMOD morphological and functional parameters were assessed by ascending aorta diameter and arterial stiffness (carotid-femoral pulse wave velocity, cfPWV)., Results: Eight hundred and four patients (34.8% women) were analyzed, age 53.1 ± 14 years; left ventricular mass index (LVMi) and E/e' ratio were impaired in 15.9 and 29.1% of cases, respectively. Dividing them into tertiles according to score: score 1 or less (30.2%); score 2-3 (47.4%); score at least 3 (22.7%). Patients identified at high risk of HFpEF (score ≥3) had higher age, BMI and blood pressure than the other two groups (P < 0.05); they showed a significantly higher prevalence of female patients (42.3%), treatment with at least two antihypertensive drugs (40.1%), diabetes (7.1%), and dyslipidemia (28%; P < 0.05), with a larger ascending aorta diameter (35.5 ± 5.5 mm, P < 0.05) and higher cfPWV (8.8 ± 2.4 m/s, P < 0.05)., Conclusion: At least one in five hypertensive patients, referred to an outpatient echocardiographic examination, has C-HMOD compatible with a high-risk category of HFpEF and have a significant increase in V-HMOD. This reinforces the notion that arterial hypertension and HFpEF are not two distinctly separate conditions but a continuum of pathophysiologic alterations., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Multiple myeloma (MM) affects a population with a high prevalence of cardiovascular (CV) disease. These patients benefit from an accurate CV risk evaluation in order to choose the safest drug regimen. Haemodynamic forces (HDFs) analysis allows for the earlier detection of myocardial damage compared with standard markers; the role played by MM in HDFs alteration, with or without the influence of hypertension, is yet to be studied. Therefore, we aimed to identify differences in HDFs analysis in patients with MM, hypertension or both versus normotensive non-oncologic subjects. A total of 173 patients (MM hypertensive patients, MMHT; MM normotensive patients, MMNT; non-oncologic hypertensive patients, CoHT; and non-oncologic normotensive patients, CoNT) underwent transthoracic echocardiography for HDFs analysis and pulse wave velocity (PWV) assessment. Hypertensive patients (MMHT, CoHT) showed decreased ejection fraction (EF), global longitudinal strain (GLS) and HDFs values compared with CoNT, whereas ventricular mass (LVMi) and PWV increased. MMNT displayed a significant reduction in systolic HDFs ( p < 0.006) and systolic ejection HDFs ( p < 0.008) compared with CoNT, without significant change in EF, GLS, LVMi or PWV. In conclusion, MM leads to ventricular remodelling regardless of hypertension; HDFs application for MM patients could help detect early myocardial damage, especially in patients receiving cardiotoxic drugs.

Introduction : Non-ischemic dilated cardiomyopathy (NIDCM) is characterized by a reduced left ventricular (LV) ejection fraction (LVEF, <50%) and a high risk for heart failure (HF) and death. Echocardiography-derived hemodynamic forces (HDFs) may provide important information on LV mechanics, but their prognostic value is unknown. Aim : To explore the features of echocardiography-derived HDFs in NIDCM and their association with clinical endpoints. Methods : Asymptomatic, non-hospitalized NIDCM patients free from coronary artery disease and moderate or severe valvular heart disease were included in this single-center observational retrospective longitudinal study. Those with atrial fibrillation and a follow-up <12 months were excluded. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause death, HF hospitalization, and ambulatory intravenous diuretics administration. LV HDFs were analyzed with a prototype software. Apex-base (HDFs-ab), lateral-septal (HDFs-ls), and HDFs-angle were computed. Results : Ninety-seven patients were included, sixty-seven (69%) were males, mean age was 62 ± 14 years, and mean LVEF was 39.2 ± 8.6%. During a median follow-up of 4.2 (3.1-5.1) years, 19 (20%) patients experienced MACE. These patients had a higher HDFs-angle (71.0 (67.0-75.0) vs. 68.0 (63.0-71.0)°, p = 0.005), lower HDFs-ls (1.36 (1.01-1.85) vs. 1.66 ([1.28-2.04])%, p = 0.015), but similar HDFs-ab (5.02 (4.39-6.34) vs. 5.66 (4.53-6.78)%, p = 0.375) compared to those without MACE. in a Cox regression analysis, HDFs-angle (HR 1.16 (95%-CI 1.04-1.30), p = 0.007) was associated with MACE, while other conventional echocardiography parameters, including LVEF and LV longitudinal strain, were not. Conclusions : HDFs-angle is associated with clinical endpoints in NIDCM. A higher HDFs-angle may be a marker of impaired myocardial performance in patients with reduced LVEF.

Purpose: Neurogenic orthostatic hypotension (nOH) is a frequent nonmotor feature of Parkinson's disease (PD), associated with adverse outcomes. Recently, 24-h ambulatory blood pressure monitoring (ABPM) showed good accuracy in diagnosing nOH. This study aims at evaluating the prognostic role of ABPM-hypotensive episodes in predicting PD disability milestones and mortality and comparing it to the well-defined prognostic role of bedside nOH., Methods: Patients with PD who underwent ABPM from January 2012 to December 2014 were retrospectively enrolled and assessed for the development of falls, fractures, dementia, bed/wheelchair confinement, hospitalization, and mortality, during an up-to-10-year follow-up. Significant ABPM-hypotensive episodes were identified when greater than or equal to two episodes of systolic BP drop ≥ 15 mmHg (compared with the average 24 h) were recorded during the awakening-to-lunch period., Results: A total of 99 patients (74% male, age 64.0 ± 10.1 years, and PD duration 6.4 ± 4.0 years) were enrolled. At baseline, 38.4% of patients had ABPM-hypotensive episodes and 46.5% had bedside nOH. On Kaplan-Meier analysis, patients with ABPM-hypotensive episodes showed earlier onset of falls (p = 0.001), fractures (p = 0.004), hospitalizations (p = 0.009), bed/wheelchair confinement (p = 0.032), dementia (p = 0.001), and shorter survival (8.0 versus 9.5 years; p = 0.009). At Cox regression analysis (adjusted for age, disease duration, Charlson Comorbidity Index, and Hoehn and Yahr stage) a significant association was confirmed between ABPM-hypotensive episodes and falls [odds ratio (OR) 3.626; p = 0.001), hospitalizations (OR 2.016; p = 0.038), and dementia (OR 2.926; p = 0.008), while bedside nOH was only associated with falls (OR 2.022; p = 0.039) and dementia (OR 1.908; p = 0.048)., Conclusions: The presence of at least two ABPM-hypotensive episodes independently predicted the development of falls, dementia, and hospitalization, showing a stronger prognostic value than the simple bedside assessment., (© 2024. Springer-Verlag GmbH Germany.)

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., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

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-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/m 2 ) versus Carfilzomib-lenalidomide-dexamethasone (target dose of K 27 mg/m 2 ) 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.

Purpose: We sought to estimate the impact of cardiovascular autonomic neuropathy (cAN) on informal caregivers of patients with Parkinson's disease (PD), defined as individuals providing regular care to a friend, partner, or family member with PD, and to evaluate the mutual relationship between caregiver burden and patient health-related quality of life (HRQoL)., Methods: We enrolled 36 consecutive patients with PD and their informal caregivers. Patients underwent a detailed motor, autonomic, cognitive, and functional assessment. Caregivers were assessed using the Zarit Burden Interview (ZBI). Differences in caregiver burden, expressed by the ZBI score, and strength of association between caregiver burden, cAN, and HRQoL were assessed using analysis of covariance (ANCOVA), logistic regression, and linear regression analyses. Analyses were adjusted for patients' age, PD duration, and motor and cognitive disability, as well as caregivers' age., Results: Moderate-severe caregiver burden was reported in 41.7% of PDcAN + versus 8.7% of PDcAN - (p < 0.001). The ZBI score was increased in PDcAN + versus PDcAN - (31.5 ± 3.4 versus 15.2 ± 2.3; p < 0.001), with tenfold higher odds (p = 0.012) of moderate-severe caregiver burden in PDcAN + , even after adjusting for potential confounders. The ZBI score correlated with cAN severity (p = 0.005), global autonomic impairment (p = 0.012), and HRQoL impairment (p < 0.001)., Conclusion: These results highlight the significant impact of cAN on PD caregivers and the need for targeted interventions addressing this frequently overlooked and insufficiently treated source of nonmotor disability in PD., (© 2022. The Author(s).)

Introduction: While autonomic failure is a well-known prognostic factor for more aggressive disease progression in Parkinson's disease (PD), with a three- to sevenfold higher risk of dementia and death within 10 years after the diagnosis, the individual impact of cardiovascular, gastrointestinal, urogenital, thermoregulatory, and pupillomotor autonomic domains on PD clinical outcomes remains unclear., Objectives: We sought to determine the 5-year risk of developing dementia, falls, postural instability, dysarthria, and dysphagia in PD patients with and without autonomic impairment at baseline and to assess the joint and individual association of each autonomic domain on these key functional outcomes. In addition, we aimed to determine the impact of each autonomic domain on activities of daily living (ADLs) and health-related quality of life (HRQoL)., Methods: We enrolled 65 consecutive PD patients in a 5-year cohort study involving standardized evaluations of autonomic symptoms, orthostatic hypotension, and motor and non-motor features, including cognitive function. Associations were estimated as odds ratio and adjusted for PD duration, age, and baseline motor impairment., Results: Cardiovascular dysautonomia was associated with a sevenfold higher risk of developing dementia (95%CI: 1.154-50.436; p = 0.035) and a fivefold higher risk of falls (95%CI: 1.099-18.949; p = 0.039), as well as significantly higher impairment in ADLs (p = 0.042) and HRQoL (p = 0.031). No relevant associations were found between the other autonomic domains and these outcomes., Conclusions: Cardiovascular dysautonomia, but not other domains, showed an association with worse 5-year clinical outcomes in PD. Our data suggest a specific role for cardiovascular autonomic dysregulation in the pathogenic mechanisms of PD progression., (© 2022. The Author(s).)

Background: Autonomic failure (AF) complicates Parkinson's disease (PD) in one-third of cases, resulting in complex blood pressure (BP) abnormalities. While autonomic testing represents the diagnostic gold standard for AF, accessibility to this examination remains limited to a few tertiary referral centers., Objective: The present study sought to investigate the accuracy of a machine learning algorithm applied to 24-h ambulatory BP monitoring (ABPM) as a tool to facilitate the diagnosis of AF in patients with PD., Methods: Consecutive PD patients naïve to vasoactive medications underwent 24 h-ABPM and autonomic testing. The diagnostic accuracy of a Linear Discriminant Analysis (LDA) model exploiting ABPM parameters was compared to autonomic testing (as per a modified version of the Composite Autonomic Symptom Score not including the sudomotor score) in the diagnosis of AF., Results: The study population consisted of n = 80 PD patients (33% female) with a mean age of 64 ± 10 years old and disease duration of 6.2 ± 4 years. The prevalence of AF at the autonomic testing was 36%. The LDA model showed 91.3% accuracy (98.0% specificity, 79.3% sensitivity) in predicting AF, significantly higher than any of the ABPM variables considered individually (hypotensive episodes = 82%; reverse dipping = 79%; awakening hypotension = 74%)., Conclusion: LDA model based on 24-h ABPM parameters can effectively predict AF, allowing greater accessibility to an accurate and easy to administer test for AF. Potential applications range from systematic AF screening to monitoring and treating blood pressure dysregulation caused by PD and other neurodegenerative disorders., (© 2022. The Author(s).)

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/m 2 , 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/m 2 , 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Vallelonga, Cesareo, Menon, Airale, Leone, Astarita, Mingrone, Tizzani, Lupia, Veglio and Milan.)

The potential relevance of blood flow for describing cardiac function has been known for the past 2 decades, but the association of clinical parameters with the complexity of fluid motion is still not well understood. Hemodynamic force (HDF) analysis represents a promising approach for the study of blood flow within the ventricular chambers through the exploration of intraventricular pressure gradients. Previous experimental studies reported the significance of invasively measured cardiac pressure gradients in patients with heart failure. Subsequently, advances in cardiovascular imaging allowed noninvasive assessment of pressure gradients during progression and resolution of ventricular dysfunction and in the setting of resynchronization therapy. The HDF analysis can amplify mechanical abnormalities, detect them earlier compared with conventional ejection fraction and strain analysis, and possibly predict the development of cardiac remodeling. Alterations in HDFs provide the earliest signs of impaired cardiac physiology and can therefore transform the existing paradigm of cardiac function analysis once implemented in routine clinical care. Until recently, the HDF investigation was possible only with contrast-enhanced echocardiography and magnetic resonance imaging, precluding its widespread clinical use. A mathematical model, based on the first principle of fluid dynamics and validated using 4-dimensional-flow-magnetic resonance imaging, has allowed HDF analysis through routine transthoracic echocardiography, making it more readily accessible for routine clinical use. This article describes the concept of HDF analysis and reviews the existing evidence supporting its application in several clinical settings. Future studies should address the prognostic importance of HDF assessment in asymptomatic patients and its incorporation into clinical decision pathways.

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 ± 1.96 and 7.72 ± 1.95 m/s, respectively. Mean difference between devices was 0.15 ± 0.56 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 ± 0.63 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., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Airale, Vallelonga, Forni, Leone, Magnino, Avenatti, Iannaccone, Astarita, Mingrone, Cesareo, Giordana, Omedè, Moretti, Veglio, Pedrizzetti and Milan.)

Competing Interests: Competing interests: None declared.

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 β2-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 ± 47 vs. 94 ± 24 g/m2; P = 0.010) and PWV (10.20 ± 2.99 vs. 8.63 ± 1.88 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., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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 ± 23 and 78 ± 13 mmHg, respectively, giving a central pulse pressure (cPP inv) of 68 ± 21 mmHg. Proximal aortic diameter was 34.9 ± 19.4 mm, whereas Z-score was -0.3 ± 1.7. 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 (β = -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., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mingrone, Astarita, Airale, Maffei, Cesareo, Crea, Bruno, Leone, Avenatti, Catarinella, Salvini, Cetani, Gay, Bringhen, Veglio, Vallelonga and Milan.)

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.

Background: The COVID-19 pandemic caused drastic changes in healthcare and severe social restrictions. Healthcare workers (HCWs) are on the front line against the virus and have been highly exposed to pandemic-related stressors, but there are limited data on their psychological involvement for a large sample in Italy., Aims: To investigate the prevalence of anxiety, distress and burnout in HCWs of North-West Italy during the COVID-19 pandemic, and to detect potential psychosocial factors associated with their emotional response., Method: This cross-sectional, survey-based study enrolled 797 HCWs. Participants completed the Impact of Event Scale - Revised, the State-Trait Anxiety Inventory - Form Y and the Maslach Burnout Inventory; demographic, family and work characteristics were also collected. Global psychological outcome, differences among professions and independent factors associated with worst psychological outcome were assessed., Results: Almost a third of the sample had severe state anxiety and distress, high emotional exhaustion and depersonalisation, and low personal accomplishment. Distress was higher in women and nurses, whereas depersonalisation was higher in men. Family division, increased workload, job changes and frequent contact with COVID-19 were associated with worst psychological outcome. Trait anxiety was associated with significantly higher risk for developing state anxiety, distress and burnout., Conclusions: An elevated psychological burden related to the COVID-19 pandemic was observed in HCWs of North-West Italy. The identification of family and work characteristics and a psychological pre-existing condition as factors associated with worst psychological outcome may help provide a tailored, preventive, organisational and psychological approach in counteracting the psychological effects of future pandemics.

The second pandemic wave flooded Italy and Europe. There are many reasons to be concerned but, as health care workers, we want to emphasize something particular. We reacted with enormous sacrifices during the first pandemic wave, despite the uncertainty, despite the inexperience, despite the structural and managerial inadequacies (partly unavoidable). In the following months the overwhelming wave turned into a slow but continuous dripping, we had to deal with. The World Health Organization (WHO) introduced the term "pandemic fatigue" to indicate the widespread feeling of distress in the entire population as a reaction to a prolonged state of crisis whose end cannot be foreseen. Health workers are no stranger to the general population, although they perceive the world from a particular standpoint. The first concern is that doctors and nurses might not be able to make up for the flaws (largely avoidable at this point) of the health care system in case of further waves. Because the strengths are breaking down and because public support, crucial in previous months, is waning. The second concern relates to the discomfort that could affect a large part of health care workers. A state of discontent and anger never seen before between doctors and nurses is spreading all around us. The fear that "pandemic fatigue" will turn into "pandemic consumption" is real and alarming.

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.

Objectives: The prevalence of hypertensive emergencies and urgencies and of acute hypertension-mediated organ damage (aHMOD) in emergency departments is unknown. Moreover, the predictive value of symptoms, blood pressure (BP) levels and cardiovascular risk factors to suspect the presence of aHMOD is still unclear. The aim of this study was to investigate the prevalence of hypertensive emergencies and hypertensive urgencies in emergency departments and of the relative frequency of subtypes of aHMOD, as well as to assess the clinical variables associated with aHMOD., Methods: We conducted a systematic literature search on PubMed, OVID, and Web of Science from their inception to 22 August 2019. Two independent investigators extracted study-level data for a random-effects meta-analysis., Results: Eight studies were analysed, including 1970 hypertensive emergencies and 4983 hypertensive urgencies. The prevalence of hypertensive emergencies and hypertensive urgencies was 0.3 and 0.9%, respectively [odds ratio for hypertensive urgencies vs. hypertensive emergencies 2.5 (1.4-4.3)]. Pulmonary oedema/heart failure was the most frequent subtype of aHMOD (32%), followed by ischemic stroke (29%), acute coronary syndrome (18%), haemorrhagic stroke (11%), acute aortic syndrome (2%) and hypertensive encephalopathy (2%). No clinically meaningful difference was found for BP levels at presentations. Hypertensive urgency patients were younger than hypertensive emergency patients by 5.4 years and more often complained of nonspecific symptoms and/or headache, whereas specific symptoms were more frequent among hypertensive emergency patients., Conclusion: Hypertensive emergencies and hypertensive urgencies are a frequent cause of access to emergency departments, with hypertensive urgencies being significantly more common. BP levels alone do not reliably predict the presence of aHMOD, which should be suspected according to the presenting signs and symptoms.

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 ± 0.35 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.

Objective: Patients with autonomic neuropathy associated with Parkinson's disease often show reverse dipping pattern/nocturnal hypertension at 24-h ambulatory blood pressure (BP) monitoring (24-h ABPM) and diurnal orthostatic hypotension. The aim of the study was to evaluate cardiac alterations in Parkinson's disease patients with reverse dipping, in comparison with non-reverse dippers Parkinson's disease and essential hypertensive patients., Methods: A total of 26 consecutive Parkinson's disease patients with reverse dipping at 24-h ABPM and no previous history of hypertension were compared with 26 non-reverse Parkinson's disease patients matched for age, sex and 24-h mean BP, and 26 essential hypertensive patients matched for nighttime mean BP. None of the Parkinson's disease patients suffered from cardiovascular diseases or were treated with antihypertensive or antihypotensive drugs. Reverse dipping was defined by a systolic day-night BP difference less than 0% at 24-h ABPM. Left ventricular (LV) hypertrophy was defined by a LV mass index at least 115 g/m in men and at least 95 g/m in women., Results: LV mass, indexed for BSA, was significantly higher in reverse dipping than non-reverse Parkinson's disease patients (respectively 90.2 ± 25.3 vs. 77.4 ± 13.3 g/m, P = 0.04), and was similar to essential hypertensive patients (91.6 ± 24.8, P = 0.92). LV hypertrophy was detected in five reverse dipping Parkinson's disease patients and four hypertensive patients, but was not present in non-reverse Parkinson's disease patients (P = 0.046). Nocturnal BP values, nocturnal BP load, weighted BP variability and age were found to correlate with the increased LV mass index., Conclusion: Reverse dipping and nocturnal hypertension are related to higher LV mass and increased prevalence of LV hypertrophy in Parkinson's disease patients.

We sought to test the accuracy of 24-hours ambulatory blood pressure (BP) monitoring (ABPM) for the detection of orthostatic hypotension (OH) in Parkinson's disease (PD). A total of 113 patients referred for autonomic testing between January 2015 and June 2017 underwent ABPM and office BP measurements in supine and standing positions. The study population consisted of 81 males and 32 females with PD duration of 6.5 ± 4.1 years and Hoehn and Yahr staging of 1 (13.3%), 1.5 (20.4%), 2 (27.4%), 2.5 (23.9%), 3 (13.3%), and 4 (1.8%). Motor fluctuations were present in 44% of patients. The data from office BP recordings were compared to selected ABPM parameters, and the results showed an association between OH and (a) ABPM-detected hypotensive episodes (Hypo-ep) and (b) ABPM-detected awakening hypotension (Hypo-aw). Having 2 or more Hypo-ep episodes ≤15 mmHg (systolic) compared to average 24-h systolic BP [Formula: see text] yielded 75% diagnostic accuracy for OH, while the presence of at least one [Formula: see text] within 90 min after getting up [Formula: see text] yielded 93% specificity for OH. A diagnostic accuracy of 87.6% was achieved when including daytime and nighttime ABPM values, weighted BP variability, systolic and diastolic BP loads, nocturnal dipping, and postprandial hypotension in a computerized prediction algorithm. In conclusion, our findings suggest that selected ABPM parameters, such as the number of hypotensive episodes and the presence of awakening hypotension, may be used to screen patients for OH, while using a computerized prediction algorithm that includes all ABPM parameters provides the greatest diagnostic accuracy.