Arterial waveforms are altered in left ventricular systolic dysfunction. We aimed to investigate the diagnostic implications of automatically analyzed pressure waveforms and their changes over time in patients with reduced ejection fraction (EF). Arterial waveforms were recorded noninvasively using applanation tonometry in patients with heart failure with reduced ejection fraction (HFrEF) and in matched controls. Waveform parameters were analyzed with respect to the left ventricular ejection time index (LVETI), the characteristics of antegrade and reflected waves, their interaction as quantified by the augmentation index, and wave intensity, expressed as the ratio of the S and D peak intensities (SDR). Overall, 78 HFrEF patients [ejection fraction (EF) 28 ± 9%] and 78 controls (EF 66 ± 8%), matched for sex, age, presence of hypertension and diabetes, systolic and diastolic blood pressure, and heart rate, were included. All waveform parameters were statistically different between patients and controls. In receiver-operator characteristic (ROC) analysis, HFrEF patients and controls could be separated best using LVETI [area under the ROC curve (AUC) 0.897; P < 0.0001] and SDR (AUC 0.911; P < 0.0001). In newly diagnosed and treated HFrEF patients, the AUC for discrimination between HFrEF patients and controls was almost ideal (0.978; P < 0.0001), when a combination of LVETI and SDR was used. Finally, in 46 HFrEF patients with available follow-up (FU) data, concordance analysis showed a high agreement of up to 0.8 between changes in the cardiac function (e.g., using EF) and changes in several waveform parameters. Pulse waveform parameters may be useful for screening and follow-up of patients with HFrEF.NEW & NOTEWORTHY Arterial pulse waveforms carry distinct signatures of heart failure with reduced ejection fraction (HFrEF). In this study, tonometry revealed differences in waveform timing, wave reflection, and wave intensity between HFrEF patients and matched controls. Combining left ventricular ejection time index and wave intensity ratios enabled near-perfect discrimination in newly diagnosed patients and closely tracked longitudinal changes in cardiac function. These findings highlight pulse waveform analysis as a promising tool for HFrEF screening and follow-up.

Background Central systolic blood pressure (cSBP) reflects the pressure experienced by vital organs and may be more closely related to hypertensive cardiac damage than brachial SBP. Twenty‐four–hour ambulatory blood pressure monitoring provides additional insight into cardiovascular load beyond office readings. This study investigated the association of 24‐hour cSBP, measured noninvasively with a validated device, with left ventricular mass index (LVMi) and LV hypertrophy. Methods We analyzed data from 21 centers worldwide (n=2367; 45.5% women; mean age 49.5 years) participating in the International 24‐Hour Aortic Blood Pressure Consortium. Brachial and central 24‐hour SBPs were recorded using the Mobil‐O‐Graph device, calibrated by either systolic/diastolic (cSBP C1) or mean/diastolic (cSBP C2) pressure; LVMi was derived echocardiographically. BP phenotypes (normotension, isolated diastolic and systolic hypertension, and systolic‐diastolic hypertension) were based on 24‐hour brachial BPs, subdivided by cSBP. Results LVMi correlated most strongly with 24‐hour cSBP C2 (P<0.001) consistently, across sex, body mass index (BMI), age, and treatment strata. Receiver operating characteristic analysis showed superior prediction of LV hypertrophy for 24‐hour cSBP C2 (area under the curve=0.68). Both brachial BP phenotype and central SBP status were independently associated with LVMi (P=0.0045 and <0.001, respectively), without interaction. Discordant classification occurred in 14.4% of participants and was linked to higher LVMi in normotension and lower LVMi in systolic‐diastolic hypertension. Conclusions Twenty‐four–hour central SBP calibrated with oscillometric mean/diastolic pressure (cSBP C2), is more closely associated with LVMi and LV hypertrophy than brachial SBP. These findings highlight the potential clinical value of incorporating central pressure monitoring into risk assessment and hypertension management.

Abstract Background Cardiovascular disease (CVD) is a major global health challenge. Vascular ageing assessment can identify high-risk individuals for effective prevention, but the knowledge, awareness, perceptions, applications, and limitations of vascular ageing assessment in clinical and research settings are limited. This study assessed these aspects among researchers and clinicians. Methods A pilot-tested questionnaire from our previous study was distributed to clinicians and researchers. Participant’s characteristics and percentages for responses on various aspects of vascular ageing including knowledge, awareness, perceptions, applications, and limitations were reported. Results Two hundred seventy-six people completed the survey (aged 47 ± 15 years, 49.6% male, 67.0% researchers, response rate 75.4%). Findings indicated a consensus on the importance of vascular ageing in a research and clinical context. Approximately 75% acknowledged the association between vascular ageing and overall CVD risk. The group identified as most likely to benefit from vascular ageing assessment were individuals with positive family histories of CVD. There was a consensus on the potential for vascular ageing biomarkers to improve CVD risk evaluation and prevention. Over 90% believe that vascular ageing can be modified. However, less than 10% of clinicians currently measure vascular ageing in clinical settings, citing time constraints, cost and lack of guidelines as main barriers. Conclusions This study highlights the perceived value of vascular ageing measures in both research and clinical settings and identifies the challenges and limitations hindering widespread implementation. Addressing the identified challenges may facilitate the integration of vascular ageing assessments into routine clinical practice, potentially improving CVD risk stratification and patient outcomes.

BACKGROUND:Novel hypertension phenotypes are described by cross-classification of brachial and aortic SBP (brSBP/aoSBP). OBJECTIVES:The aim of this study is to examine their prevalence and age and sex-distribution, factors that potentially modulate them, and their association with left ventricular hypertrophy (LVH). METHODS:Data on 24-h ambulatory BP monitoring (ABPM) using the Mobilograph device (IEM GmbH, Stolberg, Germany) and LVH from the I nternational 24-h A mbulatory aortic B lood pressure C onsortium (i24ABC) were retrieved from 31 centers (17 countries). The population was categorized into four phenotypes; concordant systolic normotension (CSN: both SBPs normal), isolated brachial systolic hypertension (IbrSH: high brSBP/normal aoSBP), isolated aortic systolic hypertension (IaoSH: normal brSBP/high aoSBP), and concordant systolic hypertension (CSH: both SBPs high). RESULTS:In 8738 participants (age: 58.4 ± 15.1 years; 51.8% men), the prevalence of IaoSH was 7.7%, being more prevalent in men, and presenting a U-shape age-distribution in them compared to a linear distribution in females. IaoSH was associated with lower heart rate and beta-blockade medications. The prevalence of IbrSH was 6.5%, presenting an inverted U-shape age-distribution; it was higher in the presence of higher heart rate and calcium channel-blockade. In 2307 individuals with LVH data, after adjustment for age, sex, DBP, IaoSH - but not IbrSH - had 2.6 higher odds of LVH compared to CSN (95% confidence interval, 1.7-3.9) and similar to CSH. CONCLUSION:IaoSH and IbrSH amounted to almost 15% and showed specific clinic characteristics. Only IaoSH was significantly associated with LVH. Outcome-driven randomized controlled trials are needed to further investigate their clinical relevance.

Background:Highlighting arterial stiffness in Community Pharmacies (CPh) has been met with considerable interest in Portugal, Austria, and Spain. TOGETHER aims to evaluate whether empowering hypertensive subjects by determining blood pressure (BP) and vascular aging in CPh increases hypertension (HTN) control, while establishing paths of lasting cooperation between General Practitioners (GP) and CPh. Methods:TOGETHER is a cluster-randomized, prospective study in Portugal, Austria, and Spain. All consecutive subjects entering CPh will be offered BP measurement and ambulatory BP monitoring (ABPM) for those with BP ≥ 140/90 mmHg. CPh will be randomly assigned to a usual care arm (including health education for HTN). In the experimental care group, vascular aging (VA) will be additionally assessed by estimating aortic pulse wave velocity using brachial oscillometry. In this group, health education will include VA, which will also be communicated to GPs. In both groups, HTN will be treated by GPs according to usual clinical practice. A second evaluation with ABPM will be performed after 6 months, and the percentage of patients with controlled hypertension will be compared between both arms. The degree of CPh/GP interaction and patients´ adherence will be assessed through validated surveys. Discussion:Five fundamental unmet needs will be addressed by TOGETHER: 1) the lack of HTN screening programs; 2) implementation of the simpler and more informative VA concept ("Your arteries are 10 years older than you"); 3) understanding CV risk on an individual basis (individual VA) should improve patient adherence and reduce physician inertia; 4) implementation of health educational programs, combined with the concept of VA; 5) higher collaboration and development of a team-based approach to HTN care between CPh and GP. The complementary organizational settings and strengths of CPh and GP will allow TOGETHER to create new strategies for the early identification and intervention in uncontrolled HTN, encompassing both lifestyle and medical treatment, while considering social, economic, and behavioral aspects. Clinical trial registration:https://clinicaltrials.gov/, identifier FP-1533-ROD-SAL-2024-01.

Background:Cardiovascular risk is elevated in patients with COPD. Central haemodynamic measurements via wave separation analysis indicate cardiovascular risk independent of well-known limitations of peripheral blood pressure measurements, but have not yet been studied in COPD. We aimed to investigate central haemodynamics and their association with lung function in patients with COPD. Methods:In this cross-sectional evaluation of cohort studies, we used propensity score matching to compare COPD patients from the randomised ELASTIC trial (n=80) to subjects without airflow limitation and cardiovascular diseases from the Heinz Nixdorf Recall study (n=2307) and the Heinz Nixdorf Multi-Generation Study (n=2625). Central haemodynamics were measured noninvasively via wave separation analysis. Forward wave amplitude (FWA) and backward wave amplitude (BWA) were compared between patients and controls matched for age, sex, hypertension and smoking, and were assessed for associations with lung hyperinflation. Results:From the initial study cohorts, we identified 75 pairs of COPD patients and matched controls. We found greater FWA in patients than in matched controls (Cohen's d 0.423, 95% confidence interval (CI) 0.098-0.746). BWA was greater in patients than in unmatched controls (Cohen's d 0.333, 95% CI 0.104-0.562), but did not differ after matching (Cohen's d 0.128, 95% CI -0.193-0.448). On multivariable regression FWA was independently associated with hyperinflation expressed as residual volume to total lung capacity ratio (standardised β -0.188, 95% CI -0.335- -0.037) in patients with COPD. Conclusion:COPD is associated with greater FWA which may contribute to increased cardiovascular risk and appears to be correlated with the degree of hyperinflation in patients with COPD.

BACKGROUND:The extensive assessment of vascular health requires the integration of both structural and functional (hemodynamic) parameters. These are usually obtained by fragmented technologies and different signals (e.g., imaging, tonometry). In this study, we aimed to (i) develop a novel software platform that enables a combined ultrasound-based analysis of longitudinal scans of the carotid; (ii) provide an initial evaluation of its technical performance and usability. METHODS:The development of the new platform was based on two validated software medical devices, the ARCSolver and the Carotid Studio, with novel components and integration efforts. The integration was achieved through the design of a unified processing pipeline and a shared data architecture, allowing seamless interoperability between the two systems. Moreover, besides the structural ultrasound-based analysis derived by Carotid Studio (i.e., Intima-Media-Thickness and diameter), a new generalized transfer function (newGTF) was developed in order to obtain ultrasound-based aortic waveforms and the ARCSolver-based algorithms were applied to obtain hemodynamic parameters (i.e., Pulse Wave Analysis). A study was conducted to evaluate the performance of the integrated system, and of the new GTF, with repeated acquisitions on 14 healthy volunteers with pairwise ultrasound and reference tonometric acquisitions at the right common carotid artery. Accuracy of the new GTF was assessed against central pulse waveforms measured by the tonometric reference method, and precision was evaluated through the repeatability of central hemodynamic parameters. Finally, a small group of medical operators tested usability of the integrated solution. RESULTS:According to the identified aims: (i) The resulting software provides an intuitive graphical user interface that enables comprehensive carotid analysis from a single acquisition. It processes longitudinal ultrasound scans to derive local structural parameters, including diameter, and applies mathematical models combined with a machine-learning-based approach to transform diameter waveforms into aortic pressure curves; (ii) the findings demonstrated good repeatability of the functional derived parameters, correlation with the reference approach and excellent usability, confirming the system's potential for clinical and research applications. CONCLUSION:The developed integrated solution may facilitate more comprehensive vascular assessment by enabling multiple measurements to be obtained within a single software environment.

BACKGROUND AND OBJECTIVE:Arterial pulse wave analysis (PWA), a tool capable of reflecting regional hemodynamics and wave propagation characteristics, has been primarily based on tonometric measurements, while ultrasound has been used for evaluating local arterial wall mechanics. This study investigates the accuracy of aortic PWA, derived from ultrasound measurements of carotid diameter, in comparison to standard tonometry. METHODS:A sub-dataset of the FUCHSIA study (i.e., patients with fibromuscular dysplasia, matched hypertensives and matched healthy controls) with pairs of carotid ultrasound (MyLab, ESAOTE, Genoa, Italy) and tonometric (SphygmoCor CvMS, Atcor Medical) recordings were used for analyses. Ultrasound longitudinal scans were processed as follows: extraction of diameter curves (Carotid Studio, Quipu); discarding low-quality curves; transformation of diameter to local pressure curves by mathematical models; machine-learning-based transformation from carotid to aortic pulse waves; and finally, calibration of aortic pressure curves. ARCSolver algorithms (AIT) were applied to these ultrasound-based aortic pressure waveforms and the tonometry-based aortic waveforms as reference method to derive PWA parameters (e.g., heart rate (HR), central systolic pressure (cSBP) and augmentation index (AIx)) for pairwise comparison. RESULTS:In total, 74 recordings from 49 patients (51 (SD 15) years; 15 men) were used in this comparative study. Tonometry- and ultrasound-derived HR correlated well (r = 0.88) with no significant bias (mean difference 0.58 (SD 4.9) bpm). Comparable results were obtained for cSBP (r = 0.97, mean difference -3.6 (SD 4.2) mmHg) and AIx (r = 0.77, mean difference -4.2 (SD 9.1) %). CONCLUSIONS:Central PWA parameters obtained from carotid ultrasound-derived aortic pressure curves showed agreement with tonometry-based measurements and results are in line with literature.

BACKGROUND AND AIMS:Increasing evidence suggests that COVID-19 survivors experience long-term cardiovascular complications possibly through development of vascular damage. The study aimed to investigate whether accelerated vascular ageing occurs after COVID-19 infection, and if so, identify its determinants. METHODS:This prospective, multicentric, cohort study, included 34 centres in 16 countries worldwide, in 4 groups of participants-COVID-19-negative controls (ⅰ) and three groups of individuals with recent (6 ± 3 months) exposure to SARS-CoV-2: not hospitalized (ⅱ), hospitalized in general wards (ⅲ), and hospitalized in intensive care units (ⅳ). The main outcome was carotid-femoral pulse wave velocity (PWV), an established biomarker of large artery stiffness. RESULTS:2390 individuals (age 50 ± 15 years, 49.2% women) were recruited. After adjustment for confounders, all COVID-19-positive groups showed higher PWV (+0.41, +0.37, and +0.40 m/s for groups 2-4, P < .001, P = .001 and P = .003) vs. controls [PWV 7.53 (7.09; 7.97) m/s adjusted mean (95% CI)]. In sex-stratified analyses, PWV differences were significant in women [PWV (+0.55, +0.60, and +1.09 m/s for groups 2-4, P < .001 for all)], but not in men. Among COVID-19 positive women, persistent symptoms were associated with higher PWV, regardless of disease severity and cardiovascular confounders [adjusted PWV 7.52 (95% CI 7.09; 7.96) vs. 7.13 (95% CI 6.67; 7.59) m/s, P < .001]. A stable or improved PWV after 12 months was found in the COVID+ groups, whereas a progression was observed in the COVID- group. CONCLUSIONS:COVID-19 is associated with early vascular ageing in the long term, especially in women.

BACKGROUND:Carotid-femoral pulse wave velocity (PWV), a marker of arterial stiffness, is a recognized cardiovascular disease risk factor. As measuring PWV is time-consuming, reliable estimation methods have been developed, but their ability to inform cardiovascular risk prediction beyond what is achievable with current clinical risk tools is uncertain. METHODS:This study includes participants aged between 40 and 69 years from the population-based CARTaGENE cohort. PWV estimations (ePWV) were obtained using published formulas (ePWV f ) or algorithmic transformation of pulse waveforms (ePWV algo ) and 10-year cardiovascular risk for each participant was computed using the ASCVD and the SCORE-2 risk equations. Participants were followed during 10 years for major adverse cardiovascular events occurrence (MACE: cardiovascular death, myocardial infarction, stroke). Associations of ePWV f and ePWV algo with MACE were obtained using Cox models adjusted for ASCVD or SCORE-2 in the overall population and in a subpopulation representative of the ePWV f derivation cohort. RESULTS:Of 17 548 eligible participants, 2263 (12.9%) experienced a MACE during follow-up. Both ePWVf and ePWV algo were associated with MACE in unadjusted analyses, but only ePWV algo remained significant after adjustments for ASCVD [hazard ratio (HR) = 1.16 [1.09-1.22]] and SCORE-2 (HR = 1.07 [1.00-1.13]). In contrast, ePWV f was not associated with MACE after adjustment for either risk score, and only after adjustment with ASCVD when it was tested in the subpopulation representative of its derivation cohort. CONCLUSIONS:Algorithm-based PWV improved cardiovascular risk prediction beyond what is achievable from recognized risk equations, whereas the predictive ability of ePWV f may not be generalizable outside of its reference population.

BACKGROUND:Fibromuscular dysplasia (FMD) is a nonatherosclerotic, multiarterial disease with unknown aetiology. The aim of this study was to comprehensively evaluate arterial stiffness, wave reflections and local arterial wall remodelling in patients with FMD and blood pressure-matched essential hypertensives (HTN). METHODS:Carotid and aortic wave separation and wave intensity analysis was performed in patients with FMD [n = 16, (14 women)], age and blood-pressure matched HTN [n = 21, (18 women)] and age-matched healthy individuals [n = 22, (19 women)]. Carotid and aortic pressure waveforms were acquired using tonometry. Carotid blood flow and diameter were measured using B-mode and doppler respectively and aortic flow using the ARCSolver algorithm. RESULTS:Carotid backward wave amplitude was comparable between HTN and FMD 14.82 ± 4.71 vs. 13.45 ± 5.36 mmHg, P = 0.13) but higher in HTN compared to healthy individuals (11.69 ± 3.78 mmHg, P = 0.03). Carotid backward compression wave intensity [FMD -5.68 (-9.32 to 3.23), HS -6.43 (-8.58 to 3.59), HTN -8.38 (-11.46 to 5.37) mmHg*m/s3*10-2) and energy (FMD 0.33 (0.21-0.46), healthy individuals 0.35 (0.24-0.52), HTN 0.43 (0.29-0.66) mmHg*m/s2*10-2] was also higher in HTN compared to healthy individuals (P = 0.04 and 0.02) and FMD (P = 0.006 and <0.001), respectively. Aortic backward wave amplitude and wave intensity energy were higher in patients with FMD compared to healthy individuals but comparable to HTN. CONCLUSION:The results indicate that, despite similar blood pressure, wave reflections at carotid are higher in patients with essential HTN compared to FMD indicating greater flow transmission to the cerebral circulation in FMD. Second, wave reflections at aortic level are higher, potentially increasing risk of cardiovascular disease in these patients.

Background and hypothesis:Intradialytic hypotension (IDH) is a common complication during hemodialysis, associated with immediate and long-term risks. Current monitoring methods lack timely warning signals for preemptive intervention. Continuous non-invasive measurement of blood pressure providing real-time insights into hemodynamic changes might enable the early detection of impending IDH. Pulse arrival time (PAT), which can be measured non-invasively and continuously by electrocardiogram (ECG) and photoplethysmography (PPG), is inversely correlated with blood pressure and might serve as such. Thus, this study explores the feasibility of using PAT to track blood pressure changes in end-stage renal disease patients undergoing hemodialysis. Methods:A feasibility study was conducted with 44 patients [mean age 64.9 (18.1 SD) years] undergoing hemodialysis, collecting data at the Klinikum rechts der Isar of the Technical University of Munich, School of Medicine. The PAT was determined by an algorithm for detecting the R-wave in the ECG and the beginning of the pulse curve in the PPG. The study focused on changes in PAT and blood pressure during three predefined time periods of 1 hour during dialysis. Statistical analysis included equivalence testing using the TOST (two one-sided t-tests) approach, correlation analysis, and classification analysis. Results:Patients' mean systolic blood pressure (BP) was 137 (30.1 SD) mmHg, diastolic BP 68.4 (18.4 SD) mmHg and PAT 233 (42.3 SD) ms. The study revealed an inverse association between PAT and BP changes, demonstrating significant correlations [systolic/diastolic blood pressures (SBP/DBP) r = -0.45, P < .001; DBP r = -0.25, P = .003] and equivalence (inverted changes in PAT and SBP (P1 = .002 and P2 = .013) and DBP (P1 < .001 and P2 = .037), respectively). Classification analysis using relative PAT changes showed moderate results for categorizing patients as SBP decliners, risers, or stable, with an F1-score of 0.67 (sensitivity 62.7%; specificity 70.9%) and an area under the curve of 0.70 from receiver operating characteristic analysis. Conclusions:The study demonstrates that tracking BP changes using PAT as a non-invasive method in hemodialysis patients is feasible. However, the reliability of PAT measurements appears to vary among patients, indicating that this method may not be universally applicable. The observed inverse association between PAT and BP changes, especially during the start to middle phase of dialysis, highlights the potential of this technique to complement traditional monitoring methods. These exploratory findings open avenues for further research to validate the utility of PAT, particularly in predicting IDH episodes and assessing its behavior in scenarios of low BP or minimal variations.

The concept of vascular aging has emerged in recent years as a comprehensive and easily understandable way for assessing cardiovascular (CV) risk, especially in subjects whose risk is underestimated by classic risk tables. However, knowledge among clinicians is very limited, and its use in daily clinical practice is even less common. Furthermore, community pharmacies are an integral part of the healthcare systems. These are highly accessible health professionals with adequate training who deserve greater responsibility in the management of hypertension and CV risk. Simultaneously, it is noteworthy that new devices have emerged on the market that allow early vascular aging (EVA) to be measured in a simple and reliable way based on estimated pulse-wave velocity. Our objective is to describe the evidence on the role of community pharmacies in assessing EVA according to published evidence. To our knowledge, there are four studies performed in Austria, Portugal, and Spain. The main results of this review are: (1) community pharmacies have demonstrated their ability to carry out large-scale vascular age estimation in international, community-based healthcare environment; (2) the prevalence of preclinical arterial damage (EVA) in the population of pharmacy customers does not differ in subjects who spontaneously visit community pharmacies compared to the general population; (3) the determining factors of arterial stiffness are very similar in the three countries studied; (4) the estimation of pulse-wave velocity in community pharmacies simultaneously involves the determination of blood pressure, demonstrating a poor control of hypertension—both in known and unknown hypertensive patients and similarly in all three countries. The determination of EVA is not superimposable to the measurement of blood pressure and provides added value in terms of vascular risk management.

Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with adverse CV outcomes. Vascular aging (VA), which is defined as the progressive deterioration of arterial function and structure over a lifetime, is an independent predictor of both AF development and CV events. A timing identification and treatment of early VA has therefore the potential to reduce the risk of AF incidence and related CV events. A network of scientists and clinicians from the COST Action VascAgeNet identified five clinically and methodologically relevant questions regarding the relationship between AF and VA and conducted a narrative review of the literature to find potential answers. These are: (1) Are VA biomarkers associated with AF? (2) Does early VA predict AF occurrence better than chronological aging? (3) Is early VA a risk enhancer for the occurrence of CV events in AF patients? (4) Are devices measuring VA suitable to perform subclinical AF detection? (5) Does atrial-fibrillation-related rhythm irregularity have a negative impact on the measurement of vascular age? Results showed that VA is a powerful and independent predictor of AF incidence, however, its role as risk modifier for the occurrence of CV events in patients with AF is debatable. Limited and inconclusive data exist regarding the reliability of VA measurement in the presence of rhythm irregularities associated with AF. To date, no device is equipped with tools capable of detecting AF during VA measurements. This represents a missed opportunity to effectively perform CV prevention in people at high risk. Further advances are needed to fill knowledge gaps in this field.