Background Aortic stenosis (AS) is commonly associated with myocardial and systemic arterial dysfunction. We use a radial artery applanation tonometry (B-Pro) device to characterise the arterial pulse profile of patients with AS and compare them against controls.
Methods The B-Pro device was applied on the left radial artery of 117 consecutive patients, where 21 patients had AS. Baseline clinical and echocardiographic characteristics were compared. Differences in arterial pulse pressure profile were quantified by means of univariate and multivariable analyses.
Results The group with AS was older (74±14 vs 62±14 years, P<0.001) and had fewer males (38% vs 65%, P=0.025), while other baseline comorbidities were similar. From the arterial pulse profile, a higher systolic peak time (202±45 vs 152±49 ms, P<0.001), lower systolic upstroke gradient (0.35±0.10 vs 0.42±0.14 mm Hg/ms, P=0.022) and longer systolic component of the cardiac cycle (43%±7% vs 39%±5%, P=0.001) were independently associated with AS.
Conclusion The B-Pro device allows for real-time microscopic arterial pulse waveform analysis. There are significant differences between the pulse profiles of patients with AS and controls. The prognostic implications of these differences warrant further study.
- aortic stenosis
- radial applanation tonometry
- pulse wave reflection
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Aortic stenosis (AS) is increasing in prevalence as the average life expectancy continues to increase worldwide.1 2 Clinical factors associated with development of the calcific valve disease include older age, male gender, elevated serum low-density lipoprotein levels, hypertension, smoking, diabetes and metabolic syndrome.3–6 In addition, patients with a history of disorders of calcium metabolism, renal failure or mediastinal radiation are also at increased risk of AS.7 Evidence suggests that degenerative aortic valve stenosis represents a form of atherosclerotic vascular disease as the pathophysiological processes appear similar.8 9
Pulse wave analysis allows a rapid bed-side estimation of central blood pressure (BP) non-invasively, as well as estimation of indices of arterial stiffness and wave reflection.10–12 Arterial stiffness and wave reflection are significant components, which affect the function of the aortic valve. In previous studies, increased arterial stiffness and wave reflection have been determined to be important independent predictors of cardiovascular morbidity and mortality in various patient populations, including chronic kidney disease (CKD), coronary artery disease and hypertension.13–17 While the association between aortic valve sclerosis and parameters derived from pulse wave analysis has been previously established in a Western population,18 no similar studies to date on AS and pulse wave analysis have been performed.
We aim to characterise the arterial pulse profile of patients with AS compared with controls, establishing a relationship between AS and the variables derived from pulse wave analysis, including central haemodynamics and arterial stiffness.
Patients included in our study cohort were consecutive patients seen at an outpatient cardiac clinic planned for echocardiography at the National University Heart Centre, Singapore. All subjects were adults (aged >21 years) and those with prior diagnosis of significant aortic regurgitation were excluded. Written informed consent was obtained from all the study participants.
Baseline clinical and demographic characteristics were collected. Prior to echocardiography, patients had pulse wave analysed by radial artery applanation tonometry (B-Pro device) applied on the left radial artery, based on validated and published protocols (figure 1), and was performed consistently by a trained member of the study team.19 Estimated indices including central systolic, diastolic and pulse pressure were calculated by a generalised transfer function.9 10 The augmentation index (derived from the arterial pulse profile by the difference between early and late systolic peak pressure divided by the pulse pressure) was used as a surrogate measure of arterial stiffness.20
Echocardiographic studies were performed by trained sonographers, and the images reviewed by a cardiologist who was blinded to the radial applanation tonometry findings. Based on results of the echocardiography, patients were stratified into the AS group (aortic valve area <1.5 cm2) or the control group (aortic valve area ≥1.5 cm2). We compared the baseline clinical and echocardiographic characteristics of these two groups by means of appropriate Χ2 tests and t-tests for normally distributed continuous variables. Differences in arterial pulse profile were determined by univariate analysis. The significant univariate parameters were then fit into a multivariable model. The model was constructed by means of logistic regression to adjust for the confounding effect of baseline patient characteristics and to subsequently identify parameters independently associated with AS from the components of the arterial pulse profile.
All statistical analysis was performed with SPSS for Windows, V.20.0, SPSS, Chicago, Illinois, USA. A P value <0.05 was considered to be statistically significant in this study.
Baseline patient profile
Of the 117 patients studied, 21 had significant AS (aortic valve area <1.5 cm2), while 96 patients were in the control group (table 1). The patients with AS were significantly older (74±14 vs 62±14) and there were approximately half as many males. Clinical background was otherwise similar, with high prevalence of hypertension, hyperlipidaemia, diabetes, CKD and ischaemic heart disease (IHD) in both groups (table 1). Smoking rates were similar, present in about a third of both populations.
Baseline echocardiographic profile was also similar in both groups (table 1). Despite significant AS, left ventricular ejection fraction was preserved (66%±10% vs 65%±11%), while estimated pulmonary artery systolic pressure and left ventricular mass index were similar as well. Concomitant lesions affecting valves other than the aortic valve were present in a fifth of the population in both groups. Of the 21 patients studied with AS, 11 patients (52%) had severe AS (aortic valve area <1 cm2), while the remaining patients (48%) had moderate AS. All these patients were medically managed and had not undergone valvular surgery.
Arterial pulse profile
We found significant differences in the arterial pulse profile (table 2). Adjusting for the effect of age and male gender, longer systolic peak time, lower systolic upstroke gradient and longer systolic duration of the cardiac cycle were independently associated with AS (table 3). Augmentation index was notably higher in the AS group (99.8±25.5 vs 89.7±17.0), but did not appear to be a significant independent predictor in the multivariable model. We did not demonstrate significant differences in the arterial pulse profile of patients with severe AS compared with patients with moderate AS.
We found significant differences in the arterial pulse profile of subjects with AS compared with controls. The characteristic pulsus parvus et tardus (‘slow-rising’ pulse) described as a physical examination finding in patients with significant AS may be demonstrated in a patient’s arterial pulse profile. The components of a ‘slow-rising’ pulse were demonstrated to be independent predictors of AS, which included a longer systolic peak time, a gentler upstroke gradient and a longer systolic duration of cardiac cycle. The associated narrow pulse pressure of AS appeared a significant predictor in univariate analysis but not in the multivariable model. Pulsus parvus et tardus has good specificity for AS (up to 98.7%) but when subtle, may be missed by clinicians and subjected to significant interobserver variability.21 Using a pulse wave reflection device may be able to objectively and reliably quantify this sign of AS rapidly by the bedside. This may aid in the diagnosis and follow-up of patients with AS.
Of interest, not all patients with significant AS demonstrate pulsus parvus et tardus.22 In fact, the carotid upstroke had been previously shown to be normal in half of patients with severe AS, and in only 7% undergoing cardiac surgery for AS.23 24 This may mean that the presence of the characteristic pulse profile while specific for AS may not be sensitive for the disease. True enough, when comparing to studies looking at physical examination and auscultatory finding AS, pulsus parvus et tardus as well as other physical signs had good specificity but low sensitivity for AS.25
In terms of pathophysiology, AS appears to be an atherosclerotic process in the elderly.26 Evidence suggests that degenerative aortic valve stenosis represents a form of atherosclerotic vascular disease as endothelial dysfunction promoting abnormal vasomotion, increased leucocyte adhesion, platelet dysfunction and vascular inflammation.7 8 The presence of systemic atherosclerosis would manifest as increased arterial stiffness and reduced arterial compliance.27 28 In our study, we used augmentation index derived from the arterial pulse profile as a surrogate measure for arterial stiffness.29 However, while the augmentation index was significantly higher in the AS group on univariate analysis, it did not appear to be an independent predictor of AS in the multivariable model. These findings were consistent with previous studies, where arterial stiffness was not found to be associated with aortic valve calcification in a multivariate model.18 Differences found on univariate model may be due to background characteristics such as older age, which has been previously shown to be a major clinical determinant of arterial stiffness.30 Other possible causes include the relatively high rates of atherosclerotic risk factors in our study population, presumably resulting in the high prevalence of atherosclerosis in both the AS and control group, thus abolishing its utility as a predictor of AS in our population.
The use of pulse wave reflection devices which record a person’s arterial pulse profile by means of radial artery applanation tonometry are increasingly common. Besides its use in specific clinical contexts, several devices are commercially available and may be used by athletes for monitoring of sports performance, or by the general population.31 Its utility in medical diagnosis and management for patients in general is unclear. The increasing ubiquity of such devices may mean data on arterial pulse profile can become readily available to a clinician who is encountering a patient for the first time. Having demonstrated that patients with AS have a characteristic pulse profile easily defined by such devices, it may imply that these devices could have significant utility in diagnosis and management of patients with AS, especially in the setting of telemedicine.32
This study is moderately sized, and does not use a cohort from the healthy general population. Instead, the cohort comprises existing outpatients in a tertiary centre, leading to high incidences of clinical comorbidities in the study population. We did not control for differences in the indication for echocardiography in the patients studied, as it was not the focus of our study, which instead aimed to correlate echocardiographic findings with that of the arterial pulse profile from radial applanation tonometry.
The presence of significant peripheral artery disease was also not quantified in our patients, and we did not compare the difference in radial applanation tonometry between both arms. This may have affected the integrity of the measured waveforms. Furthermore, we did not stratify patients based on the severity or control of their hypertension, hyperlipidaemia, diabetes, CKD, IHD or smoking. We acknowledge that the level of control or severity of these cardiovascular risk factors would vary considerably and may contribute to alterations in their measured arterial waveform.
Our study did not demonstrate significant differences in radial applanation tonometry profile between moderate and severe AS, and was not adequately powered to demonstrate a significant difference. In addition, the device may not be able to distinguish AS from other causes of outflow obstruction, including subvalvular and supravalvular AS, as well as dynamic left ventricular outflow obstruction in hypertrophic obstructive cardiomyopathy.
This study remained exploratory in nature and further prospective study with Bland Altman analysis would be required to validate its use. Clinical outcomes and follow-up data remain to be explored, and future studies are warranted to investigate the prognostic implications of the differences in arterial pulse profile in patients with AS.
The use of a radial artery applanation tonometry device allows for real-time microscopic arterial pulse waveform analysis. There are significant differences between the pulse profiles of patients with AS and their controls, which may provide clinicians with important diagnostic and in the future, prognostic information.
The authors thank HealthSTATS for the loan of the B-Pro radial applanation tonometry device that was used in this study.
Contributors NN was involved in the data analysis and conception, writing of the manuscript and submitted the manuscript. XS was involved in the data analysis and conception and writing of the manuscript. Y-QBT was involved in the conception and writing of the manuscript. SO was involved in the data collection and analysis. GKML was involved in data analysis. WKFK was involved in the writing of the manuscript. K-KP was involved in the conception and writing of the manuscript.
Funding There was no monetary funding for this study.
Competing interests None declared.
Patient consent Obtained.
Ethics approval The study was approved by the National Healthcare Group Institutional Review Board, Singapore.
Provenance and peer review Not commissioned; externally peer reviewed.
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