44 research outputs found
Imaging calcification in aortic stenosis
BACKGROUND
Aortic stenosis is a common and potentially fatal condition in which fibro-calcific
changes within the valve leaflets lead to the obstruction of blood flow. Severe
symptomatic stenosis is an indication for aortic valve replacement and timely referral
is essential to prevent adverse clinical events. Calcification is believed to represent
the central process driving disease progression. 18F-Fluoride positron emission
tomography computed tomography (PET-CT) and CT aortic valve calcium scoring
(CT-AVC) quantify calcification activity and burden respectively. The overarching
aim of this thesis was to evaluate the applications of these techniques to the study
and management of aortic stenosis.
METHODS AND RESULTS
REPRODUCIBILITY
The scan-rescan reproducibility of 18F-fluoride PET-CT and CT-AVC were
investigated in 15 patients with mild, moderate and severe aortic stenosis who
underwent repeated 18F-fluoride PET-CT scans 3.9±3.3 weeks apart. Modified
techniques enhanced image quality and facilitated clear localization of calcification
activity. Percentage error was reduced from ±63% to ±10% (tissue-to-background
ratio most-diseased segment (MDS) mean of 1.55, bias -0.05, limits of agreement -
0·20 to +0·11). Excellent scan-rescan reproducibility was also observed for CT-AVC
scoring (mean of differences 2% [limits of agreement, 16 to -12%]).
AORTIC VALVE CALCIUM SCORE: SINGLE CENTRE STUDY
Sex-specific CT-AVC thresholds (2065 in men and 1271 in women) have been
proposed as a flow-independent technique for diagnosing severe aortic stenosis. In a
prospective cohort study, the impact of CT-AVC scores upon echocardiographic
measures of severity, disease progression and aortic valve replacement (AVR)/death
were examined. Volunteers (20 controls, 20 with aortic sclerosis, 25 with mild, 33
with moderate and 23 with severe aortic stenosis) underwent CT-AVC and
echocardiography at baseline and again at either 1 or 2-year time-points. Women
required less calcification than men for the same degree of stenosis (p<0.001).
Baseline CT-AVC measurements appeared to provide the best prediction of
subsequent disease progression. After adjustment for age, sex, peak aortic jet
velocity (Vmax) ≥ 4m/s and aortic valve area (AVA)<1 cm2, the published CT-AVC
thresholds were the only independent predictor of AVR/death (hazard ratio = 6.39,
95% confidence intervals, 2.90-14.05, p<0.001).
AORTIC VALVE CALCIUM SCORE: MULTICENTRE STUDY
CT-AVC thresholds were next examined in an international multicenter registry
incorporating a wide range of patient populations, scanner vendors and analysis
platforms. Eight centres contributed data from 918 patients (age 77±10, 60% male,
Vmax 3.88±0.90 m/s) who had undergone ECG-gated CT within 3 months of
echocardiography. Of these 708 (77%) had concordant echocardiographic
assessments, in whom our own optimum sex-specific CT-AVC thresholds (women 1377, men 2062 AU) were nearly identical to those previously published. These
thresholds provided excellent discrimination for severe stenosis (c-statistic: women
0.92, men 0.88) and independently predicted AVR and death after adjustment for
age, sex, Vmax ≥4 m/s and AVA <1 cm2 (hazards ratio, 3.02 [95% confidence
intervals, 1.83-4.99], p<0.001). In patients with discordant echocardiographic
assessments (n=210), CT-AVC thresholds predicted an adverse prognosis.
BICUSPID AORTIC VALVES
Within the multicentre study, higher continuity-derived estimates of aortic valve area
were observed in patients with bicuspid valves (n=68, 1.07±0.35 cm) compared to
those with tri-leaflet valves (0.89±0.36 cm p<0.001,). This was despite no
differences in measurements of Vmax (p=0.152), or CT-AVC scores (p=0.313). The
accuracy of AVA measurments in bicuspid valves was therefore tested against
alternative markers of disease severity. AVA measurements in bicuspid valves
demonstrated extremely weak associations with CT-AVC scores (r2=0.08, p=0.02)
and failed to correlate with downstream markers of disease severity in the valve and
myocardium and against clinical outcomes. AVA measurements in bicuspid patients
also failed to independently predict AVR/death after adjustment for Vmax ≥4 m/s,
age and gender. In this population CT-AVC thresholds (women 1377, men 2062 AU)
again provided excellent discrimination for severe stenosis.
CONCLUSIONS
Optimised 18F-fluoride PET-CT scans quantify and localise calcification activity,
consolidating its potential as a biomarker or end-point in clinical trials of novel
therapies. CT calcium scoring of aortic valves is a reproducible technique, which
provides diagnostic clarity in addition to powerful prediction of disease progression
and adverse clinical events
Cardiovascular Effects of Urocortin 2 and Urocortin 3 in Patients with Chronic Heart Failure
Aims:
Urocortin 2 and urocortin 3 may play a role in the pathophysiology of heart failure and are emerging therapeutic targets. We aimed to examine the local and systemic cardiovascular effects of urocortin 2 and urocortin 3 in healthy subjects and patients with heart failure.
Methods:
Patients with heart failure (n = 8) and age and gender-matched healthy subjects (n = 8) underwent bilateral forearm arterial blood flow measurement using forearm venous occlusion plethysmography during intra-arterial infusions of urocortin 2 (3.6–36 pmol min−1), urocortin 3 (360–3600 pmol min−1) and substance P (2–8 pmol min−1). Heart failure patients (n = 9) and healthy subjects (n = 7) underwent non-invasive impedance cardiography during incremental intravenous infusions of sodium nitroprusside (573–5730 pmol kg−1 min−1 ), urocortin 2 (36–360 pmol min−1 ), urocortin 3 (1.2–12 nmol min−1) and saline placebo.
Results:
Urocortin 2, urocortin 3 and substance P induced dose-dependent forearm arterial vasodilatation in both groups (P < 0.05 for both) with no difference in magnitude of vasodilatation between patients and healthy subjects. During systemic intravenous infusions, urocortin 3 increased heart rate and cardiac index and reduced mean arterial pressure and peripheral vascular resistance index in both groups (P < 0.01 for all). Urocortin 2 produced similar responses to urocortin 3, although increases in cardiac index and heart rate were only significant in heart failure (P < 0.05) and healthy subjects (P < 0.001), respectively.
Conclusion:
Urocortins 2 and 3 cause vasodilatation, reduce peripheral vascular resistance and increase cardiac output in both health and disease. These data provide further evidence to suggest that urocortins 2 and 3 continue to hold promise for the treatment of heart failure
Prevalence and clinical implications of valvular calcification on coronary computed tomography angiography
Computed Tomography Aortic Valve Calcium Scoring for the Assessment of Aortic Stenosis Progression
Contrast-enhanced computed tomography assessment of aortic stenosis
Abstract
Objectives Non-contrast CT aortic valve calcium scoring ignores the contribution of valvular fibrosis in aortic stenosis. We assessed aortic valve calcific and non-calcific disease using contrast-enhanced CT.
Methods This was a post hoc analysis of 164 patients (median age 71 (IQR 66–77) years, 78% male) with aortic stenosis (41 mild, 89 moderate, 34 severe; 7% bicuspid) who underwent echocardiography and contrast-enhanced CT as part of imaging studies. Calcific and non-calcific (fibrosis) valve tissue volumes were quantified and indexed to annulus area, using Hounsfield unit thresholds calibrated against blood pool radiodensity. The fibrocalcific ratio assessed the relative contributions of valve fibrosis and calcification. The fibrocalcific volume (sum of indexed non-calcific and calcific volumes) was compared with aortic valve peak velocity and, in a subgroup, histology and valve weight.
Results Contrast-enhanced CT calcium volumes correlated with CT calcium score (r=0.80, p<0.001) and peak aortic jet velocity (r=0.55, p<0.001). The fibrocalcific ratio decreased with increasing aortic stenosis severity (mild: 1.29 (0.98–2.38), moderate: 0.87 (1.48–1.72), severe: 0.47 (0.33–0.78), p<0.001) while the fibrocalcific volume increased (mild: 109 (75–150), moderate: 191 (117–253), severe: 274 (213–344) mm3/cm2). Fibrocalcific volume correlated with ex vivo valve weight (r=0.72, p<0.001). Compared with the Agatston score, fibrocalcific volume demonstrated a better correlation with peak aortic jet velocity (r=0.59 and r=0.67, respectively), particularly in females (r=0.38 and r=0.72, respectively).
Conclusions Contrast-enhanced CT assessment of aortic valve calcific and non-calcific volumes correlates with aortic stenosis severity and may be preferable to non-contrast CT when fibrosis is a significant contributor to valve obstruction