Acute rheumatic fever and rheumatic heart disease in children and adolescents in Victoria, Australia.

AIM: To describe the epidemiology and clinical profile of children and adolescents with acute rheumatic fever (ARF) and rheumatic heart disease (RHD) in Victoria, Australia. METHODS: A retrospective audit was undertaken of children and adolescents with ARF and RHD attending the Royal Children's and Monash Children's Hospitals in Victoria, Australia between 2010 and 2019. Potential cases were identified by searching multiple sources for relevant ICD-10-AM codes and keywords, then reviewed manually. For confirmed cases, we collected data on patient demographics, clinical features, comorbidities and management. RESULTS: Of 179 participants included, there were 108 Victorian residents and 71 non-Victorian residents. 126 had at least one episode of ARF during the study period and 128 were diagnosed with RHD. In the Victorian resident group, the overall incidence of ARF was 0.8 per 100 000 5-14 year olds. This incidence was higher in Victorian Aboriginal and/or Torres Strait Islander (3.8 per 100 000) and Pacific Islander (32.1 per 100 000) sub-populations. Of 83 Victorian residents who had an ARF episode, 11 (13%) had a recurrence. Most Victorian residents with RHD had mixed aortic and mitral valve pathology (69.4%) and moderate to severe disease (61.9%). Most non-Victorian residents were Aboriginal and/or Torres Strait Islander people (80.3%) and were commonly transferred for tertiary or surgical management of RHD (83.1%). CONCLUSIONS: ARF and RHD continue to affect the health of significant numbers of children and adolescents living in Victoria, including severe and recurrent disease. Specialised services and a register-based control program may help to prevent complications and premature death.

Association of left ventricular motion and central augmentation index in healthy young men.

BACKGROUND: Central blood pressure is a determinant of cardiovascular outcome; however, it can be described by parameters other than systolic and diastolic pressure with central augmentation index (AIx) often utilized. Although generally considered as determined by peripheral pressure wave reflection, not all data are consistent with this interpretation of AIx. We hypothesized that the motion of the heart during systole may influence central pressure waveform morphology, including the AIx. METHOD: We studied the carotid pressure waveform, aortic stiffness and endothelial function in 20 healthy young men (full data available in 19). Arterial stiffness was measured by carotid femoral pulse wave velocity (cfPWV), endothelial function by peripheral arterial plethysmography (PAPl) and central blood pressure waveform by carotid applanation tonometry. Basal cardiac motion was assessed with pulsed wave tissue Doppler imaging of the septal mitral annulus. RESULTS: Carotid AIx decreased after the administration of glyceryl trinitrate by 11.3 ± (sem) 4.6% (P = 0.02); however, time to the inflection point (Ti) did not change. During systolic contraction at both baseline and after glyceryl trinitrate, time to peak annular systolic velocity was directly related to, and always preceded, carotid Ti (R(2) = 0.81; P < 0.01). Carotid Ti and AIx were not related to cfPWV or endothelial function. CONCLUSION: In fit young men, rather than only being a consequence of arterial properties Ti, and therefore central AIx, may be substantially determined by left ventricular systolic function. These findings question the interpretation of central AIx as a measure of pressure wave reflection and aortic stiffness and potentially impact its interpretation in diagnosis and treatment of cardiovascular risk.

Cardiac and sympathetic activation are reduced in children with Down syndrome and sleep disordered breathing.

STUDY OBJECTIVES: Sleep disordered breathing (SDB) occurs at an increased incidence in children with Down Syndrome (DS) compared to the general pediatric population. We hypothesized that, compared with typically developing (TD) children with SDB, children with DS have a reduced cardiovascular response with delayed reoxygenation after obstructive respiratory events, and reduced sympathetic drive, providing a potential explanation for their increased risk of pulmonary hypertension. DESIGN: Beat-by-beat heart rate (HR) was analyzed over the course of obstructive events (pre, early, late, post-event) and compared between groups. Also compared were the time for oxygen resaturation post-event and overnight urinary catecholamines. SETTING: Pediatric sleep laboratory. PATIENTS: Sixty-four children aged 2-17 y referred for investigation of SDB (32 DS; 32 TD) matched for age and obstructive apnea/hypopnea index. MEASUREMENT AND RESULTS: Children underwent overnight polysomnography with overnight urine collection. Compared to TD children, those with DS had significantly reduced HR changes post-event during NREM (DS: 21.4% ± 1.8%, TD: 26.6% ± 1.6%, change from late to post-event, P < 0.05). The time to resaturation post-event was significantly increased in the DS group (P < 0.05 for both NREM and REM sleep). Children with DS had significantly reduced overnight urinary noradrenaline (P < 0.01), adrenaline (P < 0.05) and dopamine levels (P < 0.01) compared with TD children. CONCLUSION: Children with DS and SDB exhibit a compromised acute cardio-respiratory response and dampened sympathetic response to SDB compared with TD children with SDB. These data may reflect autonomic dysfunction in children with DS that may place them at increased risk for cardiovascular complications such as pulmonary hypertension.

Computed tomography stress myocardial perfusion imaging in patients considered for revascularization: a comparison with fractional flow reserve.

AIMS: Adenosine stress computed tomography myocardial perfusion imaging (CTP) is an emerging non-invasive method for detecting myocardial ischaemia. Its value when compared with fractional flow reserve (FFR), a highly accurate index of ischaemia, is unknown. Our aim was to determine the diagnostic accuracy of CTP and its incremental value when used with computed tomography coronary angiography (CTA) for detecting ischaemia compared with FFR. METHODS AND RESULTS: Forty-two patients (126 vessel territories), who had at least one ≥50% angiographic stenosis on invasive angiography considered for non-urgent revascularization, were included and underwent FFR and CT assessment, including CTP, delayed contrast enhancement scan and CTA all acquired using 320-detector row CT, and prospective ECG gating. Fractional flow reserve was determined in 86 territories subtended by vessels with ≥50% stenosis upon visual assessment. Fractional flow reserve ≤0.8 was considered to indicate significant ischaemia. Computed tomography myocardial perfusion imaging correctly identified 31/41 (76%) ischaemic territories and 38/45 (84%) non-ischaemic territories. Per-vessel territory sensitivity, specificity, positive, and negative predictive values of CTP were 76, 84, 82, and 79%, respectively. The combination of a ≥50% stenosis on CTA and perfusion defect on CTP was 98% specific for ischaemia, while the presence of <50% stenosis on CTA and normal perfusion on CTP was 100% specific for exclusion of ischaemia. Mean radiation for CTP and combined CT was 5.3 and 11.3 mSv, respectively. CONCLUSION: Computed tomography myocardial perfusion imaging is moderately accurate in identifying perfusion defects associated with ischaemia as assessed by FFR in patients considered for revascularization. In territories, where CTA and CTP are concordant, CTA/CTP is highly accurate in the detection and exclusion of ischaemia. This is achievable with acceptable radiation exposure using 320-detector row CT and prospective ECG gating.

Increased sympathetic activity in children with obstructive sleep apnea: cardiovascular implications.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased sympathetic activity and hypertension in adults. We tested the hypothesis that children with OSA also have increased sympathetic activity as measured by overnight urinary catecholamines, and that this increase is related to the severity of OSA and to blood pressure (BP). METHODS: Seventy snoring children referred for assessment of sleep disordered breathing and 26 healthy non-snoring control children (age range: 3-12 years, 59 M/37 F) were studied. Overnight polysomnography was performed coincident with a 12h overnight urine collection. Urinary catecholamine levels were determined using high performance liquid chromatography (noradrenaline, adrenaline and dopamine, with levels adjusted for creatinine excretion). Simple linear and stepwise multiple linear regressions were used to determine the independent associations between catecholamine levels and age, gender, BMI z-score, systolic BP z-score, diastolic BP z-score, and apnea hypopnea index (AHI). RESULTS: Simple linear regressions revealed significant associations between noradrenaline and AHI (r = 0.32) and age (r = -0.20, p < 0.05 for both). Significant associations were also found between adrenaline and AHI (r = 0.27) and age (r = -0.25, p < 0.05 for both). Systolic BP z-score and diastolic z-score were both significantly associated with adrenaline (r = 0.22 and r = 0.20 respectively, p < 0.05 for both). Multivariate analysis revealed that only AHI was a significant independent predictor of noradrenaline (model R(2) = 0.10, p = 0.001). Similarly, only AHI and age were significant independent predictors of adrenaline (model R(2) = 0.12, p < 0.05). CONCLUSIONS: This study demonstrates that levels of overnight urinary noradrenaline and adrenaline are related to the severity of OSA in children. These data indicate that children with OSA have increased sympathetic tone that may contribute to the cardiovascular consequences of the condition.

Diagnostic accuracy of noninvasive coronary angiography with 320-detector row computed tomography.

We sought to evaluate the diagnostic accuracy of noninvasive coronary angiography using 320-detector row computed tomography, which provides 16-cm craniocaudal coverage in 350 ms and can image the entire coronary tree in a single heartbeat, representing a significant advance from previous-generation scanners. We evaluated 63 consecutive patients who underwent 320-detector row computed tomography and invasive coronary angiography for the investigation of suspected coronary artery disease. Patients with known coronary artery disease were excluded. Computed tomographic (CT) studies were assessed by 2 independent observers blinded to results of invasive coronary angiography. A single observer unaware of CT results assessed invasive coronary angiographic images quantitatively. All available coronary segments were included in the analysis, regardless of size or image quality. Lesions with >50% diameter stenoses were considered significant. Mean heart rate was 63 ± 7 beats/min, with 6 patients (10%) in atrial fibrillation during image acquisition. Thirty-three patients (52%) and 70 of 973 segments (7%) had significant coronary stenoses on invasive coronary angiogram. Seventeen segments (2%) were nondiagnostic on computed tomogram and were assumed to contain significant stenoses on an "intention-to-diagnose" analysis. Sensitivity, specificity, and positive and negative predictive values of computed tomography for detecting significant stenoses were 94%, 87%, 88%, and 93%, respectively, by patient (n = 63), 89%, 95%, 82%, and 97%, respectively, by artery (n = 260), and 87%, 97%, 73%, and 99%, respectively, by segment (n = 973). In conclusion, noninvasive 320-detector row CT coronary angiography provides high diagnostic accuracy across all coronary segments, regardless of size, cardiac rhythm, or image quality.

The heart rate response to spontaneous arousal from sleep is reduced in children with Down syndrome referred for evaluation of sleep-disordered breathing.

Arousal from sleep in healthy adults is associated with a large, transient increase in heart rate (HR). Individuals with Down syndrome (DS) have attenuated cardiovascular responses to autonomic tests during wakefulness. We tested the hypothesis that the HR response to arousal from sleep is reduced in children with DS and obstructive sleep apnea (OSA) compared with healthy children. Twenty children aged 3-17 yr referred for investigation of sleep-disordered breathing (10 DS, and 10 OSA controls) matched for age and obstructive apnea/hypopnea index underwent routine overnight polysomnography. In addition, 10 nonsnoring controls from the general community were studied. Beat-by-beat HR was analyzed from 15 s pre- to 15 s post-spontaneous arousals and compared between groups using two-way ANOVA with repeated measures. Data are presented as means + or - SE. For both rapid eye movement (REM) and non-REM (NREM), arousals were associated with a significant increase in HR in all groups (peak response NREM: DS, 118 + or - 1% at 3 s; OSA controls, 124 + or - 2% at 4 s; and healthy controls, 125 + or - 3% at 4 s; and peak response REM: DS, 116 + or - 2% at 4 s; OSA controls, 123 + or - 3% at 4 s; and healthy controls, 125 + or - 4 at 4 s; P < 0.001 for all). Post hoc analysis revealed that HR in the DS group was significantly lower than both control groups at 1-4 s in NREM and at 4 to 5 s in REM (P < 0.05 for all). In conclusion, the HR response to spontaneous arousal from sleep is reduced in children with DS and OSA compared with healthy children. This attenuated cardiovascular response could be due to reduced sympathetic activation or blunted vagal withdrawal and may have implications for the child with DS and OSA.

Cardiovascular magnetic resonance-derived aortic distensibility: validation and observed regional differences in the elderly.

OBJECTIVE: Applanation tonometry evaluation of pulse wave velocity is widely accepted as the 'gold standard' method for noninvasively assessing arterial stiffness. Newer noninvasive tools such as cardiovascular magnetic resonance can also evaluate arterial stiffness, but have not been validated. The aim of this study was to validate cardiovascular magnetic resonance-derived aortic distensibility with pulse wave velocity and to investigate age-related changes in regional aortic distensibility. METHODS: Ten young (20-30 years) and ten old (60-70 years) patients underwent applanation tonometry assessment of pulse wave velocity. Cardiovascular magnetic resonance measurements of arterial stiffness were evaluated by aortic distensibility (10-3 mmHg-1) at three separate locations, the ascending aorta, proximal descending aorta and distal descending aorta. RESULTS: Pulse wave velocity correlated strongly with aortic distensibility measurements at each site: ascending aorta R2 = 0.57, proximal descending aorta R2 = 0.60 and distal descending aorta R2 = 0.72. As expected, the old cohort had significantly increased aortic stiffness compared with the young cohort (P < 0.01). Post-hoc comparison showed an increase in proximal stiffness in the old cohort compared with the young cohort (P = 0.018). CONCLUSION: Cardiovascular magnetic resonance-derived aortic distensibility is an accurate measure of arterial stiffness and can evaluate regional stiffness through the aorta. Furthermore, our results suggest that aortic stiffening may preferentially occur in the proximal aortic segments in the elderly.

Quantitative and qualitative changes in the resting electrocardiograph after percutaneous transluminal septal myocardial ablation for the treatment of symptomatic obstructive hypertrophic cardiomyopathy.

Percutaneous Transluminal Septal Myocardial Ablation (PTSMA) may reduce symptoms in patients with obstructive hypertrophic cardiomyopathy. Limited quantitative and qualitative data exists on the effects of PTSMA on the resting electrocardiograph. We report repolarisation and conduction abnormalities and incidence of arrhythmia post-PTSMA. Twelve-lead electrocardiographs from subjects without pre-procedural pacemakers who underwent successful procedures (37 procedures, mean age 61+/-14 years) were analysed for rhythm, heart rate, PR and QTc intervals, QRS duration and left or right bundle branch block (RBBB, LBBB). Four subjects developed permanent complete AV block, 19 subjects developed new RBBB and two subjects developed new LBBB pre-discharge. At a median follow-up of 34 (range 1-84) months, no new AV block, ventricular arrhythmias or deaths occurred. Post-PTSMA PR, QRS and QTc intervals lengthened (PR 180+/-33 ms, 204+/-40 ms, QRS 105+/-20 ms, 132+/-27 ms and QTc 454+/-32 ms, 491+/-37 ms (pre- and post-PTSMA respectively, all p=0.001). Predictors of permanent complete AV block included female gender (p=0.013), older age (p=0.013) and pre-existing LBBB (p<0.001). Atrio-ventricular and intra-ventricular conduction disturbances are common post-PTSMA. A pre-existing LBBB is a risk factor for the development of complete AV block and may merit prophylactic pacemaker insertion.

Arterial transfer functions and the reconstruction of central aortic waveforms: myths, controversies and misconceptions.

Continuing reports in the literature regarding the potential of central pulse wave analysis in clinical practice and a recent consensus statement demonstrate the increasing interest in the clinical application of arterial transfer functions. A number of misconceptions, however, persist regarding their use. In spite of ongoing controversy, there are considerable published data that would permit users to assess the validity and accuracy of the technique. We provide a comprehensive review of available data, all of which appear to be clear and consistent. The technique does not permit accurate reconstruction of central waveforms from entirely non-invasively acquired data. We should move on from the misconception that what is being studied is central aortic data when transfer functions are applied non-invasively, and accept that it is radial waveform data that have been passed through a single mathematical transformation. We have a readily applicable, non-invasive and reproducible technique for acquiring radial waveform data, with or without the application of a generalized arterial transfer function. We must explore the potential of this technique in an analytical manner, and without untenable preconceptions, if we are to learn the secrets that it may yet reveal.

'Generalizability' of a radial-aortic transfer function for the derivation of central aortic waveform parameters.

OBJECTIVE: Arterial transfer functions (TFs) describe the relationship between the pressure waveform at different arterial sites. Generalized TFs are used to reconstruct central aortic waveforms from non-invasively obtained peripheral waveforms and have been promoted as potentially clinically useful. A limitation is the paucity of information on their 'generalizability' with no information existing on the number of subjects required to construct a satisfactory TF, nor is adequate prospective validation available. We therefore investigated the uniformity of radial-aortic TFs and prospectively estimated the capacity of a generalized TF to reconstruct individual central blood pressure parameters. PATIENTS AND METHODS: Ninety-three subjects (64 male) were studied by simultaneous radial applanation and high-fidelity (Millar Mikro-tip catheter) direct measurement of central aortic BP during elective coronary procedures. Subjects were prospectively randomized to either a derivation or validation group. RESULTS: Increasing numbers of individual TFs from the derivation group were averaged to form a generalized TF. There was minimal change with greater than 20 TFs averaged. In the validation group, the error in most reconstructed parameters related to the absolute value of the directly measured parameter [systolic blood pressure (SBP) and pulse pressure, P<0.05; systolic pressure-time interval, subendocardial viability index, augmentation index, and times to the inflection point, peak and end systole, all P<0.01]. Aorto-radial delay was related to error in reconstructed central aortic SBP and pulse pressure (negatively) and time to peak systole (positively) (all P<0.001). Reconstruction of augmentation index was poor. DISCUSSION: Inclusion of more than 20 individual TFs in the construction of a generalized TF does not improve 'generalizability'. There appear to be systematic errors in derived central pressure waveforms and derived aortic augmentation index is inaccurate compared to the directly measured value.

Arterial pulse wave velocity but not augmentation index is associated with coronary artery disease extent and severity: implications for arterial transfer function applicability.

OBJECTIVES: The aim of this study was to test the hypothesis that coronary artery disease extent and severity are associated with central aortic pressure waveform characteristics. BACKGROUND: Although it is thought that central aortic pressure waveform characteristics, particularly augmentation index, may influence cardiovascular disease progression and predict cardiovascular risk, little is known of the relationship between central waveform characteristics and the severity and extent of coronary artery disease. METHODS: Central aortic waveforms (2F Millar pressure transducer-tipped catheters) were acquired at the time of coronary angiography for suspected native coronary artery disease in 40 patients (24 male). The severity and extent of disease were assessed independently by two observers using two previously described scoring systems (modified Gensini's stenosis and Sullivan's extent scores). Relationships between disease scores, aortic waveform characteristics, aorto-radial pulse wave velocity and subject demographic features were assessed by regression techniques. RESULTS: Both extent and severity scores were associated with increasing age and male sex (P < 0.001), but no other risk factors. Both scores were independently associated with aorto-radial pulse wave velocity (P < 0.001), which entered a multiple regression model prior to age and sex. This association was not dependent upon blood pressure. Neither score was associated with central aortic augmentation index, by either simple or multiple linear regression techniques including heart rate, subject demographic features and cardiovascular risk factors. CONCLUSIONS: Aorto-radial pulse wave velocity, but not central aortic augmentation index, is associated with both the extent and severity of coronary artery disease. This has potentially important implications for applicability of a generalized arterial transfer function.

Drug effects on the mechanical properties of large arteries in humans.

1. Arteries become stiffer with increasing age and various disease states. A complete description of arterial mechanical properties in vivo is not possible, although a number of methods have been used. 2. Detailed discussion in the present review is limited to pulse wave velocity and estimates of central waveform morphology derived by the application of a generalized arterial transfer function. 3. Many drugs affect these parameters, either increasing or decreasing apparent stiffness. However, the extent to which changes reflect changes in blood pressure rather than more fundamental vessel wall properties remains unclear. Similarly, it is as yet unknown whether determining the need for, or assessing the effectiveness of, drug treatment by the assessment of arterial mechanical properties will offer any advantage and the usefulness of these techniques as routine clinical tools remains to be established.

Formation of ovarian follicular fluid may be due to the osmotic potential of large glycosaminoglycans and proteoglycans.

During mammalian follicle development, a fluid-filled antrum develops in the avascular centre of the follicle. We investigated the hypothesis that follicular fluid contains osmotically-active molecules, sufficiently large so as to not freely escape the follicular fluid. Such molecules could generate an osmotic differential and thus recruit fluid from the surrounding vascularised stroma into the antrum. Follicular fluid was collected from bovine follicles classified histologically as healthy (n = 4 pools) or atretic (n = 4 pools). Dialysis of the follicular fluid at 300 kDa or 500 kDa resulted in a reduction in colloid osmotic pressure of 35% and 60%, respectively, in fluid from healthy follicles and 29% and 80% from atretic follicles. Digestion of follicular fluid with Streptomyces hyaluronidase, chondroitinase ABC or DNase 1 followed by dialysis resulted in reductions in osmotic pressure of 43%, 53% and 43% respectively for fluids from healthy follicles and 34%, 20% and 31% for atretic follicles. Digestion with collagenase I, proteinase K, heparanase 1 or keratanase had no significant effect on the osmotic pressure of follicular fluid of healthy follicles. Ion exchange and size exclusion, Western blotting and ELISA identified the proteoglycans versican and inter-alpha trypsin inhibitor and the glycosaminoglycan hyaluronan in follicular fluid. We conclude that these molecules or aggregates of them are of sufficient size to contribute to the osmotic potential of follicular fluid and thus recruit fluid into the follicular antrum. DNA may also contribute but it is probably not a component that is regulated for this role.

Acute and chronic effects of flavanol-rich cocoa on vascular function in subjects with coronary artery disease: a randomized double-blind placebo-controlled study.

Evidence suggests that flavonoid-containing diets reduce cardiovascular risk, but the mechanisms responsible are unclear. In the present study, we sought to determine the effect of flavanol-rich cocoa on vascular function in individuals with CAD (coronary artery disease). Forty subjects (61+/-8 years; 30 male) with CAD were recruited to a 6-week randomized double-blind placebo-controlled study. Subjects consumed either a flavanol-rich chocolate bar and cocoa beverage daily (total flavanols, 444 mg/day) or matching isocaloric placebos daily (total flavanols, 19.6 mg/day) for 6 weeks. Brachial artery FMD (flow-mediated dilation) and SAC (systemic arterial compliance) were assessed at baseline, 90 min following the first beverage and after 3 and 6 weeks of daily consumption. Soluble cellular adhesion molecules and FBF (forearm blood flow) responses to ACh (acetylcholine chloride; 3-30 microg/min) and SNP (sodium nitroprusside; 0.3-3 microg/min) infusions, forearm ischaemia and isotonic forearm exercise were assessed at baseline and after 6 weeks. FMD, SAC and FBF responses did not differ between groups at baseline. No acute or chronic changes in FMD or SAC were seen in either group. No difference in soluble cellular adhesion molecules, FBF responses to ischaemia, exercise, SNP or ACh was seen in the group receiving flavanol-rich cocoa between baseline and 6 weeks. These data suggest that over a 6-week period, flavanol-rich cocoa does not modify vascular function in patients with established CAD.

Systemic inflammatory markers in acute coronary syndrome: association with cardiovascular risk factors and effect of early lipid lowering.

BACKGROUND: Evidence for statin therapy in prevention of coronary artery disease is overwhelming. In spite of theoretical benefits, any additional advantage of its early introduction in the management of acute coronary syndrome is, however, uncertain. We therefore investigated differences between plasma levels of the systemic inflammatory markers intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, C-reactive protein and interleukin-6 in patients presenting with unstable angina or acute myocardial infarction, and assessed whether the 30-day levels of these markers are influenced by early instigation of the HMG-CoA reductase inhibitor pravastatin. MATERIALS AND METHODS: 170 (134 male) patients presenting with acute coronary syndrome, but without previous statin therapy, participated. Blood was taken within 24 h of onset of ischaemic pain and again at 30 days. In all, 87 (71 male) participants were treated with pravastatin (20-40 mg daily) and 83 (63 male) with a matched placebo. RESULTS: At presentation, interleukin-6 was higher in males than in females (P=0.008) and lower in those with a pre-existing history of myocardial infarction (P=0.038). C-reactive protein and interleukin-6 were greater in myocardial infarction, but this difference was lost at 30 days. Thirty-day changes in all parameters were inversely related to level at presentation but not to treatment with pravastatin. Hypertension (P=0.011) and smoking (P=0.042) were associated with elevation of C-reactive protein with no difference between unstable angina or acute myocardial infarction. The effect of these individual factors was cumulative. CONCLUSIONS: Interleukin-6 was greater in acute myocardial infarction than in unstable angina; E-selectin was positively associated with a previous myocardial infarction and inversely related to age. We found no effect of early introduction of pravastatin on systemic inflammatory markers 30 days after acute coronary syndrome.

Waveform dispersion, not reflection, may be the major determinant of aortic pressure wave morphology.

The objective of this study was to investigate the determinants of aortic pressure waveform morphology in the thoracoabdominal aorta with specific reference to features of potential prognostic value for cardiovascular disease. In particular, we aimed to determine the location of major pressure wave reflection sites within the aorta. Aortic pressure waveforms were acquired with 2-Fr Millar Mikro-tip catheter transducers in 40 subjects (26 men, 14 women), and repeated in 10 subjects, at five predetermined points within the aorta: aortic root, transverse arch, and at the levels of the diaphragm, renal arteries, and aortic bifurcation. Waveforms were analyzed for augmentation index (AI), time to inflection point (Ti), and pressure parameters. AI decreased progressively between the aortic root and bifurcation (P < 0.001), and Ti increased (P < 0.01). There was the expected progressive peripheral amplification of systolic and pulse pressures and fall in time to peak pressure (all P < 0.001). There was no difference on repeat pullback or between sexes. These data are at variance with the concept that central AI results solely from pressure wave reflection, when Ti would be expected to decrease and AI increase with distal progression. Pressure wave propagation phenomena may contribute, and the potential role of frequency dispersion merits investigation.