Arterial pulse wave modeling and analysis for vascular-age studies: a review from VascAgeNet.

Arterial pulse waves (PWs) such as blood pressure and photoplethysmogram (PPG) signals contain a wealth of information on the cardiovascular (CV) system that can be exploited to assess vascular age and identify individuals at elevated CV risk. We review the possibilities, limitations, complementarity, and differences of reduced-order, biophysical models of arterial PW propagation, as well as theoretical and empirical methods for analyzing PW signals and extracting clinically relevant information for vascular age assessment. We provide detailed mathematical derivations of these models and theoretical methods, showing how they are related to each other. Finally, we outline directions for future research to realize the potential of modeling and analysis of PW signals for accurate assessment of vascular age in both the clinic and in daily life.

When right ventricular pressure meets volume: The impact of arrival time of reflected waves on right ventricle load in pulmonary arterial hypertension.

Right ventricular (RV) wall tension in pulmonary arterial hypertension (PAH) is determined not only by pressure, but also by RV volume. A larger volume at a given pressure generates more wall tension. Return of reflected waves early after the onset of contraction, when RV volume is larger, may augment RV load. We aimed to elucidate: (1) the distribution of arrival times of peak reflected waves in treatment-naïve PAH patients; (2) the relationship between time of arrival of reflected waves and RV morphology; and (3) the effect of PAH treatment on the arrival time of reflected waves. Wave separation analysis was conducted in 68 treatment-naïve PAH patients. In the treatment-naïve condition, 54% of patients had mid-systolic return of reflected waves (defined as 34-66% of systole). Despite similar pulmonary vascular resistance (PVR), patients with mid-systolic return had more pronounced RV hypertrophy compared to those with late-systolic or diastolic return (RV mass/body surface area; mid-systolic return 54.6 ± 12.6 g m-2 , late-systolic return 44.4 ± 10.1 g m-2 , diastolic return 42.8 ± 13.1 g m-2 ). Out of 68 patients, 43 patients were further examined after initial treatment. At follow-up, the stiffness of the proximal arteries, given as characteristic impedance, decreased from 0.12 to 0.08 mmHg s mL-1 . Wave speed was attenuated from 13.3 to 9.1 m s-1 , and the return of reflected waves was delayed from 64% to 71% of systole. In conclusion, reflected waves arrive at variable times in PAH. Early return of reflected waves was associated with more RV hypertrophy. PAH treatment not only decreased PVR, but also delayed the timing of reflected waves. KEY POINTS: Right ventricular (RV) wall tension in pulmonary arterial hypertension (PAH) is determined not only by pressure, but also by RV volume. Larger volume at a given pressure causes larger RV wall tension. Early return of reflected waves adds RV pressure in early systole, when RV volume is relatively large. Thus, early return of reflected waves may increase RV wall tension. Wave reflection can provide a description of RV load. In PAH, reflected waves arrive back at variable times. In over half of PAH patients, the RV is exposed to mid-systolic return of reflected waves. Mid-systolic return of reflected waves is related to RV hypertrophy. PAH treatment acts favourably on the RV not only by reducing resistance, but also by delaying the return of reflected waves. Arrival timing of reflected waves is an important parameter for understanding the relationship between RV load and its function in PAH.

Right atrial function is associated with right venticular diastolic stiffness: RA-RV interaction in pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) patients have altered right atrial (RA) function and right ventricular (RV) diastolic stiffness. This study assessed the impact of RV diastolic stiffness on RA-RV interaction. METHODS: PAH patients with low or high end-diastolic elastance (Eed) (n=94) were compared with controls (n=31). Treatment response was evaluated in 62 patients. RV and RA longitudinal strain, RA emptying and RV filling were determined and diastole was divided into a passive and active phase. Vena cava backflow was calculated as RA active emptying-RV active filling and RA stroke work as RA active emptying×RV end-diastolic pressure. RESULTS: With increased Eed, RA and RV passive strain were reduced while active strain was preserved. In comparison to controls, patients had lower RV passive filling but higher RA active emptying and RA stroke work. RV active filling was lower in patients with high Eed, resulting in higher vena cava backflow. Upon treatment, Eed was reduced in ~50% of the patients with high Eed, which coincided with larger reductions in afterload, RV mass and vena cava backflow and greater improvements in RV active filling and stroke volume in comparison with patients in whom Eed remained high. CONCLUSIONS: In PAH, RA function is associated with changes in RV function. Despite increased RA stroke work, severe RV diastolic stiffness is associated with reduced RV active filling and increased vena cava backflow. In 50% of patients with high baseline Eed, diastolic stiffness remained high, despite treatment. A reduction in Eed coincided with a large reduction in afterload, increased RV active filling and decreased vena cava backflow.

Validity and success rate of noninvasive mean arterial blood pressure measurements in cf-LVAD patients: A technical review.

BACKGROUND: The life expectancy of patients with a continuous flow left ventricular assist device (cf-LVAD) is increasing. Adequate determination and regulation of mean arterial pressure (MAP) is important to prevent adverse events. Given the low pulsatility characteristics in these patients, standard blood pressure equipment is inadequate to monitor MAP and not recommended. We provide an overview of currently available noninvasive techniques, using an extensive search strategy in three online databases (Pubmed, Scopus and Google Scholar) to find validation studies using invasive intra-arterial blood pressure measurement as a reference. Mean differences with the reference values smaller than 5 ± 8 mm Hg were considered acceptable. OBSERVATIONS: After deduplication, screening, and exclusion of incorrect sources, eleven studies remained with 3139 successful MAP measurements in 386 patients. Four noninvasive techniques, using Doppler, pulse oximetry, finger cuff volume clamp, or slow upper arm cuff deflation, were identified and evaluated for validity and success rate in cf-LVAD patients. Here, a comprehensive technical background of the blood pressure measurement methods is provided in combination with a clinical use comparison. Of the reported noninvasive techniques, slow cuff devices performed most optimally (mean difference 1.3 ± 5.2 mm Hg). CONCLUSIONS: Our results are encouraging and indicate that noninvasive blood pressure monitoring options with acceptable validity and success rate are available. Further technical development and validation is warranted for the growing population of patients on long-term cf-LVAD support.

Estimation of Intraglomerular Pressure Using Invasive Renal Arterial Pressure and Flow Velocity Measurements in Humans.

BACKGROUND: Glomerular hyperfiltration resulting from an elevated intraglomerular pressure (Pglom) is an important cause of CKD, but there is no feasible method to directly assess Pglom in humans. We developed a model to estimate Pglom in patients from combined renal arterial pressure and flow measurements. METHODS: We performed hemodynamic measurements in 34 patients undergoing renal or cardiac angiography under baseline conditions and during hyperemia induced by intrarenal dopamine infusion (30 µg/kg). For each participant during baseline and hyperemia, we fitted an adapted three-element Windkessel model that consisted of characteristic impedance, compliance, afferent resistance, and Pglom. RESULTS: We successfully analyzed data from 28 (82%) patients. Median age was 58 years (IQR, 52-65), median eGFR was 95 ml/min per 1.73 m2 (IQR, 74-100) using the CKD-EPI formula, 30% had microalbuminuria, and 32% had diabetes. The model showed a mean Pglom of 48.0 mm Hg (SD=10.1) at baseline. Under hyperemia, flow increased by 88% (95% CI, 68% to 111%). This resulted in a 165% (95% CI, 79% to 294%) increase in afferent compliance and a 13.1-mm Hg (95% CI, 10.0 to 16.3) decrease in Pglom. In multiple linear regression analysis, diabetes (coefficient, 10.1; 95% CI, 5.1 to 15.1), BMI (0.99 per kg/m2; 95% CI, 0.38 to 1.59), and renal perfusion pressure (0.42 per mm Hg; 95% CI, 0.25 to 0.59) were significantly positively associated with baseline Pglom. CONCLUSIONS: We constructed a model on the basis of proximal renal arterial pressure and flow velocity measurements that provides an overall estimate of glomerular pressure and afferent and efferent resistance in humans. The model provides a novel research technique to evaluate the hemodynamics of CKD on the basis of direct pressure and flow measurements. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Functional HEmodynamics in patients with and without Renal Artery stenosis (HERA), NL40795.018.12 at the Dutch national trial registry (toetsingonline.nl).

Lower complexity and higher variability in beat-to-beat systolic blood pressure are associated with elevated long-term risk of dementia: The Rotterdam Study.

INTRODUCTION: We hypothesized that subclinical disruption in blood pressure (BP) dynamics, captured by lower complexity and higher variability, may contribute to dementia risk, above and beyond BP levels. METHODS: This prospective cohort study followed 1835 older adults from 1997 to 2016, with BP complexity quantified by sample entropy and BP variability quantified by coefficient of variation using beat-to-beat BP measured at baseline. RESULTS: Three hundred thirty-four participants developed dementia over 20 years. Reduced systolic BP (SBP) complexity was associated with a higher risk of dementia (hazard ratio [HR] comparing extreme quintiles: 1.55; 95% confidence interval [CI]: 1.09-2.20). Higher SBP variability was also associated with a higher risk of dementia (HR comparing extreme quintiles: 1.57; 95% CI: 1.11-2.22. These findings were observed after adjusting for age, sex, apolipoprotein E (APOE) genotype, mean SBP, and other confounding factors. DISCUSSIONS: Our findings suggest that lower complexity and higher variability of beat-to-beat SBP are potential novel risk factors or biomarkers for dementia.

Conduit arterial wave reflection promotes pressure transmission but impedes hydraulic energy transmission to the microvasculature.

Current thinking suggests that wave reflection in arteries limits pulse pressure and hydraulic energy (HE) transmission to the microvasculature and that this protective effect reduces with advancing age. However, according to transmission line theory, pressure transmission (Tp) and reflection (R) coefficients are proportional (Tp = 1 + R), implying that wave reflection would promote rather than limit pressure transmission. We hypothesized that increasing distal pulse pressure (PPd) with age is instead related to increased proximal pulse pressure (PPp) and its forward component and that these are modulated by arterial compliance. A one-dimensional model of a fractal arterial tree containing 21 generations was constructed. Wave speed in each vessel was prescribed to achieve a uniform R at every junction, with changes in R achieved by progressively stiffening proximal or distal vessels. For both stiffening scenarios, decreasing reflection led to a decrease or no change in PPd when forward pressure or compliance were held constant, respectively, suggesting that wave reflection per se does not limit pressure transmission. Proximal pulse pressure, its forward component, and PPd increased with decreasing compliance; furthermore, proximal and distal pulse pressures were approximately proportional. With fixed compliance but decreasing reflection, HE transmission increased, whereas pressure transmission decreased, consistent with transmission line theory. In conclusion, wave reflection does not protect the microvasculature from high PPd; rather, PPp and PPd are modulated by arterial compliance, which reduces with age. Wave reflection has opposing effects on pressure and HE transmission; hence, the relative importance of pressure versus HE in contributing to microvascular damage warrants investigation.NEW & NOTEWORTHY With aging, a reduction in the stiffness gradient between elastic and muscular arteries is thought to reduce wave reflection in conduit arteries, leading to increased pulsatile pressure transmission into the microvasculature. This assumes that wave reflection limits pressure transmission in arteries. However, using a computational model, we showed that wave reflection promotes pulsatile pressure transmission, although it does limit hydraulic energy transmission. Increased microvascular pulse pressure with aging is instead related to decreasing arterial compliance.

Early return of reflected waves increases right ventricular wall stress in chronic thromboembolic pulmonary hypertension.

Pulmonary vascular resistance (PVR) and compliance are comparable in proximal and distal chronic thromboembolic pulmonary hypertension (CTEPH). However, proximal CTEPH is associated with inferior right ventricular (RV) adaptation. Early wave reflection in proximal CTEPH may be responsible for altered RV function. The aims of the study are as follows: 1) to investigate whether reflected pressure returns sooner in proximal than in distal CTEPH and 2) to elucidate whether the timing of reflected pressure is related to RV dimensions, ejection fraction (RVEF), hypertrophy, and wall stress. Right heart catheterization and cardiac MRI were performed in 17 patients with proximal CTEPH and 17 patients with distal CTEPH. In addition to the determination of PVR, compliance, and characteristic impedance, wave separation analysis was performed to determine the magnitude and timing of the peak reflected pressure (as %systole). Findings were related to RV dimensions and time-resolved RV wall stress. Proximal CTEPH was characterized by higher RV volumes, mass, and wall stress, and lower RVEF. While PVR, compliance, and characteristic impedance were similar, proximal CTEPH was related to an earlier return of reflected pressure than distal CTEPH (proximal 53 ± 8% vs. distal 63 ± 15%, P < 0.05). The magnitude of the reflected pressure waves did not differ. RV volumes, RVEF, RV mass, and wall stress were all related to the timing of peak reflected pressure. Poor RV function in patients with proximal CTEPH is related to an early return of reflected pressure wave. PVR, compliance, and characteristic impedance do not explain the differences in RV function between proximal and distal CTEPH.NEW & NOTEWORTHY In chronic thromboembolic pulmonary hypertension (CTEPH), proximal localization of vessel obstructions is associated with poor right ventricular (RV) function compared with distal localization, though pulmonary vascular resistance, vascular compliance, characteristic impedance, and the magnitude of wave reflection are similar. In proximal CTEPH, the RV is exposed to an earlier return of the reflected wave. Early wave reflection may increase RV wall stress and compromise RV function.

Vena cava backflow and right ventricular stiffness in pulmonary arterial hypertension.

Vena cava backflow is a well-recognised clinical hallmark of right ventricular failure in pulmonary arterial hypertension (PAH). Backflow may result from tricuspid regurgitation during right ventricular systole or from impaired right ventricular diastolic filling during atrial contraction. Our aim was to quantify the forward and backward flow in the vena cava and to establish the main cause in PAH.In 62 PAH patients, cardiac magnetic resonance measurements provided volumetric flows (mL·s-1) in the superior and inferior vena cava; time integration of flow gave volume. The "backward fraction" was defined as the ratio of the backward and forward volumes in the vena cava, expressed as a percentage. Time of maximum vena cava backflow was expressed as a percentage of the cardiac cycle. Right ventricular volumes and aortic stroke volume were determined. Right heart catheterisation gave right ventricular and right atrial pressures. Right ventricular end-diastolic stiffness was determined with the single-beat method.The median (interquartile range) backward fraction was 12% (3-24%) and it was >20% in 21 patients. Maximum backflow occurred at near 90% of the cardiac cycle, coinciding with atrial contraction. The backward fraction was associated with maximal right atrial pressure (Spearman's r=0.77), right ventricular end-diastolic stiffness (r=0.65) and right ventricular end-diastolic pressure (r=0.77), and was negatively associated with stroke volume (r= -0.61) (all p<0.001).Significant backward flow in the vena cava was observed in a large group of PAH patients and occurred mostly during atrial contraction as a consequence of impaired right ventricular filling due to right ventricular diastolic stiffness. The backward flow due to tricuspid regurgitation was of significance in only a small minority of patients.

The right treatment for the right ventricle.

PURPOSE OF REVIEW: Right ventricular (RV) function is an important determinant of morbidity and mortality in patients with pulmonary arterial hypertension (PAH). Although substantial progress has been made in understanding the development of RV failure in the last decennia, this has not yet resulted in the development of RV selective therapies. In this review, we will discuss the current status on the treatment of RV failure and potential novel therapeutic strategies that are currently being investigated in clinical trials. RECENT FINDINGS: Increased afterload results in elevated wall tension. Consequences of increased wall tension include autonomic disbalance, metabolic shift and inflammation, negatively affecting RV contractility. Compromised RV systolic function and low cardiac output activate renin-angiotensin aldosterone system, which leads to fluid retention and further increase in RV wall tension. This vicious circle can be interrupted by directly targeting the determinants of RV wall tension; preload and afterload by PAH-medications and diuretics, but is also possibly by restoring neurohormonal and metabolic disbalance, and inhibiting maladaptive inflammation. A variety of RV selective drugs are currently being studied in clinical trials. SUMMARY: Nowadays, afterload reduction is still the cornerstone in treatment of PAH. New treatments targeting important pathobiological determinants of RV failure directly are emerging.

Carotid Flow Augmentation, Arterial Aging, and Cerebral White Matter Hyperintensities.

Objective- Aortic stiffness and pressure wave reflection are associated with age-related cerebral microvascular disease, but the underlying mechanism remains obscure. We hypothesized that cerebral (carotid) flow alterations potentially mediate these associations. Approach and Results- Doppler waveforms were recorded in 286 patients with hypertension to measure the carotid flow augmentation index (FAIx) as the late/early-systolic velocity amplitude ratio. Tonometric waveforms were recorded to estimate the aortic pressure AIx (PAIx), aortic compliance, and carotid-femoral and carotid-radial pulse wave velocities. Additionally, white matter hyperintensities on brain magnetic resonance imaging were evaluated using the Fazekas scale. With increasing age, the carotid late systolic velocity increased, whereas the early systolic velocity decreased, although the aortic augmented pressure increased in parallel with the incident wave height ( P<0.001). Both FAIx and PAIx increased with age, but the age-dependent curves were upwardly concave and convex, respectively. FAIx increased exponentially with increasing PAIx ( r=0.71). Compared with PAIx, FAIx was more closely ( P≤0.001) correlated with the aortic pulse wave velocity, aortic compliance, and elastic/muscular pulse wave velocity ratio. FAIx was associated with white matter hyperintensities scores independently of confounders including age, sex, diabetes mellitus, hypercholesterolemia, and aortic pulse wave velocity ( P=0.01), and was more predictive of white matter hyperintensities presence than PAIx. Conclusions- Carotid FAIx had closer associations with age, aortic stiffness, and cerebral white matter hyperintensities than aortic PAIx. These results indicate that carotid flow augmentation (enhanced by aortic stiffening and pressure wave reflection from the lower body) causes microcerebrovascular injury potentially through increasing cerebral flow pulsations, but this detrimental effect is greater than that estimated from PAIx.

Detecting aortic valve stenosis based on the non-invasive blood pressure waveform-a proof of concept study.

The incidence of aortic valve stenosis (AoS) increases with age, and once diagnosed, symptomatic severe AoS has a yearly mortality rate of 25%. AoS is diagnosed with transthoracic echocardiography (TTE), however, this gold standard is time consuming and operator and acoustic window dependent. As AoS affects the arterial blood pressure waveform, AoS-specific waveform features might serve as a diagnostic tool. Aim of the present study was to develop a novel, non-invasive, AoS detection model based on blood pressures waveforms. This cross-sectional study included patients with AoS undergoing elective transcatheter or surgical aortic valve replacement. AoS was determined using TTE, and patients with no or mild AoS were labelled as patients without AoS, while patients with moderate or severe AoS were labelled as patients with AoS. Non-invasive blood pressure measurements were performed in awake patients. Ten minutes of consecutive data was collected. Several blood pressure-based features were derived, and the median, interquartile range, variance, and the 1st and 9th decile of the change of these features were calculated. The primary outcome was the development of a machine-learning model for AoS detection, investigating multiple classifiers and training on the area under the receiver-operating curve (AUROC). In total, 101 patients with AoS and 48 patients without AoS were included. Patients with AoS showed an increase in left ventricular ejection time (0.02 s, p = 0.001), a delayed maximum upstroke in the systolic phase (0.015 s, p < 0.001), and a delayed maximal systolic pressure (0.03 s, p < 0.001) compared to patients without AoS. With the logistic regression model, a sensitivity of 0.81, specificity of 0.67, and AUROC of 0.79 were found. The majority of the population without AoS was male (85%), whereas in the population with AoS this was evenly distributed (54% males). Age was significantly (5 years, p < 0.001) higher in the population with AoS. In the present study, we developed a novel model able to distinguish no to mild AoS from moderate to severe AoS, based on blood pressure features with high accuracy. Clinical registration number: The study entailing patients with TAVR treatment was registered at ClinicalTrials.gov (NCT03088787, https://clinicaltrials.gov/ct2/show/NCT03088787 ). The study with elective cardiac surgery patients was registered with the Netherland Trial Register (NL7810, https://trialsearch.who.int/Trial2.aspx?TrialID=NL7810 ).

Developing technologies to assess vascular ageing: a roadmap from VascAgeNet.

Vascular ageing is the deterioration of arterial structure and function which occurs naturally with age, and which can be accelerated with disease. Measurements of vascular ageing are emerging as markers of cardiovascular risk, with potential applications in disease diagnosis and prognosis, and for guiding treatments. However, vascular ageing is not yet routinely assessed in clinical practice. A key step towards this is the development of technologies to assess vascular ageing. In this Roadmap, experts discuss several aspects of this process, including: measurement technologies; the development pipeline; clinical applications; and future research directions. The Roadmap summarises the state of the art, outlines the major challenges to overcome, and identifies potential future research directions to address these challenges.

A white-box model for real-time simulation of acid-base balance in blood plasma.

Maintaining an optimal acid base is important for the patient. The theory underlying acid-base balance can be challenging for clinicians and educators. These considerations justify creating simulations that include realistic changes to the partial pressure of carbon dioxide, pH, and bicarbonate ion concentration in a range of conditions. Our explanatory simulation application requires a model that derives these variables from total carbon dioxide content and runs in real time. The presented model is derived from the Stewart model, which is based on physical and chemical principles, and takes into account the effects of weak acids and strong ions on the acid-base balance. An inventive code procedure allows for efficient computation. The simulation results match target data for a broad range of clinically and educationally relevant disturbances of the acid-base balance. The model code meets the real-time goals of the application and can be applied in other educational simulations. Python model source code is made available.

Cardiovascular and health cost impacts of cuff blood pressure underestimation and overestimation of invasive aortic systolic blood pressure.

OBJECTIVE: Hypertension management is directed by cuff blood pressure (BP), but this may be inaccurate, potentially influencing cardiovascular disease (CVD) events and health costs. This study aimed to determine the impact on CVD events and related costs of the differences between cuff and invasive SBP. METHODS: Microsimulations based on Markov modelling over one year were used to determine the differences in the number of CVD events (myocardial infarction or coronary death, stroke, atrial fibrillation or heart failure) predicted by Framingham risk and total CVD health costs based on cuff SBP compared with invasive (aortic) SBP. Modelling was based on international consortium data from 1678 participants undergoing cardiac catheterization and 30 separate studies. Cuff underestimation and overestimation were defined as cuff SBP less than invasive SBP and cuff SBP greater than invasive SBP, respectively. RESULTS: The proportion of people with cuff SBP underestimation versus overestimation progressively increased as SBP increased. This reached a maximum ratio of 16 : 1 in people with hypertension grades II and III. Both the number of CVD events missed (predominantly stroke, coronary death and myocardial infarction) and associated health costs increased stepwise across levels of SBP control, as cuff SBP underestimation increased. The maximum number of CVD events potentially missed (11.8/1000 patients) and highest costs ($241 300 USD/1000 patients) were seen in people with hypertension grades II and III and with at least 15 mmHg of cuff SBP underestimation. CONCLUSION: Cuff SBP underestimation can result in potentially preventable CVD events being missed and major increases in health costs. These issues could be remedied with improved cuff SBP accuracy.

Right Atrial Adaptation to Precapillary Pulmonary Hypertension: Pressure-Volume, Cardiomyocyte, and Histological Analysis.

BACKGROUND: Precapillary pulmonary hypertension (precPH) patients have altered right atrial (RA) function and right ventricular (RV) diastolic stiffness. OBJECTIVES: This study aimed to investigate RA function using pressure-volume (PV) loops, isolated cardiomyocyte, and histological analyses. METHODS: RA PV loops were constructed in control subjects (n = 9) and precPH patients (n = 27) using magnetic resonance and catheterization data. RA stiffness (pressure rise during atrial filling) and right atrioventricular coupling index (RA minimal volume / RV end-diastolic volume) were compared in a larger cohort of patients with moderate (n = 39) or severe (n = 41) RV diastolic stiffness. Cardiomyocytes were isolated from RA tissue collected from control subjects (n = 6) and precPH patients (n = 9) undergoing surgery. Autopsy material was collected from control subjects (n = 6) and precPH patients (n = 4) to study RA hypertrophy, capillarization, and fibrosis. RESULTS: RA PV loops showed 3 RA cardiac phases (reservoir, passive emptying, and contraction) with dilatation and elevated pressure in precPH. PrecPH patients with severe RV diastolic stiffness had increased RA stiffness and worse right atrioventricular coupling index. Cardiomyocyte cross-sectional area was increased 2- to 3-fold in precPH, but active tension generated by the sarcomeres was unaltered. There was no increase in passive tension of the cardiomyocytes, but end-stage precPH showed reduced number of capillaries per mm2 accompanied by interstitial and perivascular fibrosis. CONCLUSIONS: RA PV loops show increased RA stiffness and suggest atrioventricular uncoupling in patients with severe RV diastolic stiffness. Isolated RA cardiomyocytes of precPH patients are hypertrophied, without intrinsic sarcomeric changes. In end-stage precPH, reduced capillary density is accompanied by interstitial and perivascular fibrosis.

Sex Differences in Blood Pressure and Potential Implications for Cardiovascular Risk Management.

BACKGROUND: Accurate blood pressure (BP) measurement is critical for optimal cardiovascular risk management. Age-related trajectories for cuff-measured BP accelerate faster in women compared with men, but whether cuff BP represents the intraarterial (invasive) aortic BP is unknown. This study aimed to determine the sex differences between cuff BP, invasive aortic BP, and the difference between the 2 measurements. METHODS: Upper-arm cuff BP and invasive aortic BP were measured during coronary angiography in 1615 subjects from the Invasive Blood Pressure Consortium Database. This analysis comprised 22 different cuff BP devices from 28 studies. RESULTS: Subjects were 64±11 years (range 40-89) and 32% women. For the same cuff systolic BP (SBP), invasive aortic SBP was 4.4 mm Hg higher in women compared with men. Cuff and invasive aortic SBP were higher in women compared with men, but the sex difference was more pronounced from invasive aortic SBP, was the lowest in younger ages, and the highest in older ages. Cuff diastolic blood pressure overestimated invasive diastolic blood pressure in both sexes. For cuff and invasive diastolic blood pressure separately, there were sex*age interactions in which diastolic blood pressure was higher in younger men and lower in older men, compared with women. Cuff pulse pressure underestimated invasive aortic pulse pressure in excess of 10 mm Hg for both sexes in older age. CONCLUSIONS: For the same cuff SBP, invasive aortic SBP was higher in women compared with men. How this translates to cardiovascular risk prediction needs to be determined, but women may be at higher BP-related risk than estimated by cuff measurements.

Noninvasive continuous arterial blood pressure monitoring with Nexfin®.

BACKGROUND: If invasive measurement of arterial blood pressure is not warranted, finger cuff technology can provide continuous and noninvasive monitoring. Finger and radial artery pressures differ; Nexfin® (BMEYE, Amsterdam, The Netherlands) measures finger arterial pressure and uses physiologic reconstruction methodologies to obtain values comparable to invasive pressures. METHODS: Intra-arterial pressure (IAP) and noninvasive Nexfin arterial pressure (NAP) were measured in cardiothoracic surgery patients, because invasive pressures are available. NAP-IAP differences were analyzed during 30 min. Tracking was quantified by within-subject precision (SD of individual NAP-IAP differences) and correlation coefficients. The ranges of pressure change were quantified by within-subject variability (SD of individual averages of NAP and IAP). Accuracy and precision were expressed as group average ± SD of the differences and considered acceptable when smaller than 5 ± 8 mmHg, the Association for the Advancement of Medical Instrumentation criteria. RESULTS: NAP and IAP were obtained in 50 (34-83 yr, 40 men) patients. For systolic, diastolic, mean arterial, and pulse pressure, median (25-75 percentiles) correlation coefficients were 0.96 (0.91-0.98), 0.93 (0.87-0.96), 0.96 (0.90-0.97), and 0.94 (0.85-0.98), respectively. Within-subject precisions were 4 ± 2, 3 ± 1, 3 ± 2, and 3 ± 2 mmHg, and within-subject variations 13 ± 6, 6 ± 3, 9 ± 4, and 7 ± 4 mmHg, indicating precision over a wide range of pressures. Group average ± SD of the NAP-IAP differences were -1 ± 7, 3 ± 6, 2 ± 6, and -3 ± 4 mmHg, meeting criteria. Differences were not related to mean arterial pressure or heart rate. CONCLUSION: Arterial blood pressure can be measured noninvasively and continuously using physiologic pressure reconstruction. Changes in pressure can be followed and values are comparable to invasive monitoring.