Uncovering the treatable burden of severe aortic stenosis in the UK.

OBJECTIVE: To estimate the population prevalence and treatable burden of severe aortic stenosis (AS) in the UK. METHODS: We adapted a contemporary model of the population profile of symptomatic and asymptomatic severe AS in Europe and North America to estimate the number of people aged ≥55 years in the UK who might benefit from surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI). RESULTS: With a point prevalence of 1.48%, we estimate that 291 448 men and women aged ≥55 years in the UK had severe AS in 2019. Of these, 68.3% (199 059, 95% CI 1 77 201 to 221 355 people) would have been symptomatic and, therefore, more readily treated according to their surgical risk profile; the remaining 31.7% of cases (92 389, 95% CI 70 093 to 144 247) being asymptomatic. Based on historical patterns of intervention, 58.4% (116 251, 95% CI 106 895 to 1 25 606) of the 199 059 symptomatic cases would qualify for SAVR, with 7208 (95% CI 7091 to 7234) being assessed as being in a high, preoperative surgical risk category. Among the remaining 41.6% (82 809, 95% CI 73 453 to 92 164) of cases potentially unsuitable for SAVR, an estimated 61.7% (51 093, 95% CI 34 780 to 67 655) might be suitable for TAVI. We estimate that 172 859 out of 291 448 prevalent cases of severe AS (59.3%) will subsequently die within 5 years without proactive management. CONCLUSIONS: These data suggest a high burden of severe AS in the UK requiring surgical or transcatheter intervention that challenges the ongoing capacity of the National Health Service to meet the needs of those affected.

Iodine-123 metaiodobenzylguanidine scintigraphy for the assessment of cardiac sympathetic innervation and the relationship with cardiac autonomic function in healthy adults using standardized methods.

BACKGROUND: Global iodine-123 metaiodobenzylguanidine (I-MIBG) uptake is predictive of cardiovascular events and mortality in patients with heart failure. Normal variations in global and regional uptake, however, are not well defined and few studies have addressed the functional relevance of I-MIBG uptake and distribution in healthy individuals. MATERIALS AND METHODS: We performed I-MIBG scintigraphy and cardiac autonomic function testing using the standardized methodology in 15 healthy individuals (mean age 54.6±5.3 years, male : female 10 : 5) with no evidence of previous myocardial infarction or ischaemic heart disease. RESULTS: Early heart to mediastinum ratio (HMR) was 1.67±0.13, late HMR was 1.73±0.16 and washout rate was 19.09±7.63% (4.20-31.30). Regional analysis showed reduced tracer uptake at the apex, base and inferior wall in all individuals. Early and late HMR correlated negatively with RFa (r=-0.603; P=0.05 and r=-0.644; P=0.033) and expiration and inspiration ratio (r=-0.616; P=0.043 and r=-0.676; P=0.022) and positively with LFa/RFa (r=0.711; P=0.014 and r=0.784; P=0.004). Washout rate correlated only with RFa (r=0.642; P=0.033). CONCLUSION: Healthy adults show a heterogeneous pattern of cardiac innervation with reduced regional uptake of I-MIBG. Furthermore, HMR correlates with indices of cardiac sympathetic function, suggesting that it might not only be a useful prognostic marker but may also provide insight into the functional integrity of the cardiac autonomic nervous system.

Multiparametric cardiovascular magnetic resonance assessment of cardiac allograft vasculopathy.

OBJECTIVES: This study sought to evaluate the diagnostic performance of multiparametric cardiovascular magnetic resonance (CMR) for detecting cardiac allograft vasculopathy (CAV) using contemporary invasive epicardial artery and microvascular assessment techniques as reference standards, and to compare the performance of CMR with that of angiography. BACKGROUND: CAV continues to limit the long-term survival of heart transplant recipients. Coronary angiography has a Class I recommendation for CAV surveillance and annual or biannual surveillance angiography is performed routinely in most centers. METHODS: All transplant recipients referred for surveillance angiography at a single UK center over a 2-year period were prospectively screened for study eligibility. Patients prospectively underwent coronary angiography followed by coronary intravascular ultrasound, fractional flow reserve, and index of microcirculatory resistance. Within 1 month, patients underwent multiparametric CMR, including assessment of regional and global ventricular function, absolute myocardial blood flow quantification, and myocardial tissue characterization. In addition, 10 healthy volunteers underwent CMR. RESULTS: Forty-eight patients were recruited, median 7.1 years (interquartile range: 4.6 to 10.3 years) since transplantation. The CMR myocardial perfusion reserve was the only independent predictor of both epicardial (ß = -0.57, p < 0.001) and microvascular disease (ß = -0.60, p < 0.001) on stepwise multivariable regression. The CMR myocardial perfusion reserve significantly outperformed angiography for detecting moderate CAV (area under the curve, 0.89 [95% confidence interval (CI): 0.79 to 1.00] vs. 0.59 [95% CI: 0.42 to 0.77], p = 0.01) and severe CAV (area under the curve, 0.88 [95% CI: 0.78 to 0.98] vs. 0.67 [95% CI: 0.52 to 0.82], p = 0.05). CONCLUSIONS: CAV, including epicardial and microvascular components, can be detected more accurately using noninvasive CMR-based absolute myocardial blood flow assessment than with invasive coronary angiography, the current clinical surveillance technique.

Comprehensive validation of cardiovascular magnetic resonance techniques for the assessment of myocardial extracellular volume.

BACKGROUND: Extracellular matrix expansion is a key element of ventricular remodeling and a potential therapeutic target. Cardiovascular magnetic resonance (CMR) T1-mapping techniques are increasingly used to evaluate myocardial extracellular volume (ECV); however, the most widely applied methods are without histological validation. Our aim was to perform comprehensive validation of (1) dynamic-equilibrium CMR (DynEq-CMR), where ECV is quantified using hematocrit-adjusted myocardial and blood T1 values measured before and after gadolinium bolus; and (2) isolated measurement of myocardial T1, used as an ECV surrogate. METHODS AND RESULTS: Whole-heart histological validation was performed using 96 tissue samples, analyzed for picrosirius red collagen volume fraction, obtained from each of 16 segments of the explanted hearts of 6 patients undergoing heart transplantation who had prospectively undergone CMR before transplantation (median interval between CMR and transplantation, 29 days). DynEq-CMR-derived ECV was calculated from T1 measurements made using a modified Look-Locker inversion recovery sequence before and 10 and 15 minutes post contrast. In addition, ECV was measured 2 to 20 minutes post contrast in 30 healthy volunteers. There was a strong linear relationship between DynEq-CMR-derived ECV and histological collagen volume fraction (P<0.001; within-subject: r=0.745; P<0.001; r(2)=0.555 and between-subject: r=0.945; P<0.01; r(2)=0.893; for ECV calculated using 15-minute postcontrast T1). Correlation was maintained throughout the entire heart. Isolated postcontrast T1 measurement showed significant within-subject correlation with histological collagen volume fraction (r=-0.741; P<0.001; r(2)=0.550 for 15-minute postcontrast T1), but between-subject correlations were not significant. DynEq-CMR-derived ECV varied significantly according to contrast dose, myocardial region, and sex. CONCLUSIONS: DynEq-CMR-derived ECV shows a good correlation with histological collagen volume fraction throughout the whole heart. Isolated postcontrast T1 measurement is insufficient for ECV assessment.

Patent foramen ovale--assessment and treatment.

A patent foramen ovale (PFO) is detectable in 20-25% of the population. Some, but not all, case control studies have found an increased incidence of PFO in patients with cryptogenic stroke. Prospective cohort studies have failed to convincingly demonstrate a link between PFO and first stroke, and evidence linking PFO to recurrent stroke is far from compelling. The rate of recurrent stroke in medically treated patients is low, but the development of devices for PFO closure has lead to enthusiasm in some quarters to pursue a strategy of device closure. Nonrandomized studies have suggested a lower risk of recurrent events with device closure but the data are heterogeneous, and potentially prone to bias. Device implantation is associated with a risk of major adverse events of between 1.5% and 2.3%, and there is a significant rate of failure to close shunts. The results of randomized trials of device closure are keenly awaited. Migraine with aura has been linked with PFO. A recent metanalysis suggested an association, but the one prospective population study did not. The well-publicized and controversial MIST Trial is the only randomized trial of device closure in migraineurs yet published, and failed to demonstrate a convincing benefit from device closure. Other conditions such as platypnea-orthodeoxia syndrome and prevention of decompression sickness in divers, may justify device closure. Evidence for a role of PFO in the etiology of cryptogenic stroke and migraine is contradictory. It is possible that some patients might benefit from PFO closure but there is scant evidence of sufficient quality to justify routine PFO closure in either group. It is essential that ongoing randomized trials of device closure are completed.

Comparison of real-time three-dimensional echocardiography with cardiovascular magnetic resonance for left ventricular volumetric assessment in unselected patients.

AIMS: To compare left ventricular (LV) volume indices and the ejection fraction (EF) obtained using real-time three-dimensional echocardiography (RT3DE) and cardiovascular magnetic resonance (CMR) in unselected patients representative of 'real-world' clinical practice, and to determine the effect of RT3DE image quality on these parameters. METHODS AND RESULTS: Sixty consecutive patients undergoing CMR underwent same day RT3DE. LV volume and EF measurements were made using both modalities and compared. All scans were independently analysed by a second observer to assess inter-observer variability, and 40% were re-analysed to assess intra-observer variability. RT3DE image quality was graded as good, adequate, and non-analysable. Thirteen (22%) patients had good RT3DE image quality, 29 (48%) had adequate image quality, and 18 (30%) had image quality precluding analysis. Body mass index and arrhythmia frequency were higher in patients with suboptimal image quality. RT3DE significantly underestimated end-diastolic volume (EDV) (-45 ± 35 mL, P < 0.001), end-systolic volume (ESV) (-11 ± 24 mL, P = 0.004), and EF (-7 ± 9%, P < 0.001) compared with CMR although the degree of underestimation was substantially less when image quality was good. Eleven patients (18%) classified as having a normal EF by CMR had a reduced EF according to RT3DE, all but one of which had suboptimal image quality. Observer variability for RT3DE was higher than for CMR for all parameters, however, the difference was not significant when RT3DE image quality was good. CONCLUSIONS: In contrast to previously published data from highly selected patient groups, 'real-world' RT3DE substantially underestimates LV volumes and EF. The degree of underestimation is related to image quality.

The echocardiographic assessment of functional mitral regurgitation.

Functional mitral regurgitation (MR) is common, clinically important, and mechanistically complex. Its assessment by echocardiography can be challenging, and particular care is needed in the quantification of severity. Echocardiographers need to be aware of the potential limitations of flow convergence and vena contracta methods in assessing severity and alert to the prognostic importance of even moderate functional MR. Three-dimensional echocardiography has the potential to improve both the understanding of the mechanisms of functional MR and the accuracy of its quantification.

Impact of pressure recovery on echocardiographic assessment of asymptomatic aortic stenosis: a SEAS substudy.

OBJECTIVES: The aim of this analysis was to assess the diagnostic importance of pressure recovery in evaluation of aortic stenosis (AS) severity. BACKGROUND: Although pressure recovery has previously been demonstrated to be particularly important in assessment of AS severity in groups of patients with moderate AS or small aortic roots, it has never been evaluated in a large clinical patient cohort. METHODS: Data from 1,563 patients in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) study was used. Inner aortic diameter was measured at annulus, sinus, sinotubular junction, and supracoronary level. Aortic valve area index (AVAI) was calculated by continuity equation and pressure recovery and pressure recovery adjusted AVAI (energy loss index [ELI]), by validated equations. Primarily, sinotubular junction diameter was used to calculate pressure recovery and ELI, but pressure recovery and ELI calculated at different aortic root levels were compared. Severe AS was identified as AVAI and ELI < or =0.6 cm(2)/m(2). Patients were grouped into tertiles of peak transaortic velocity. RESULTS: Pressure recovery increased with increasing peak transaortic velocity. Overestimation of AS severity by unadjusted AVAI was largest in the lowest tertile and if pressure recovery was assessed at the sinotubular junction. In multivariate analysis, a larger difference between AVAI and ELI was associated with lower peak transaortic velocity (beta = 0.35) independent of higher left ventricular ejection fraction (beta = -0.049), male sex (beta = -0.075), younger age (beta = 0.093), and smaller aortic sinus diameter (beta = 0.233) (multiple R(2) = 0.18, p < 0.001). Overall, 47.5% of patients classified as having severe AS by AVAI were reclassified to nonsevere AS when pressure recovery was taken into account. CONCLUSIONS: For accurate assessment of AS severity, pressure recovery adjustment of AVA must be routinely performed. Estimation of pressure recovery at the sinotubular junction is suggested.

Three-dimensional echocardiography is superior to multiplane transoesophageal echo in the assessment of regurgitant mitral valve morphology.

AIMS: Transoesophageal echocardiography (TOE) plays a vital role in the assessment of mitral valve morphology. However, the accuracy of TOE may be limited by inadequate recognition of all segments. We aimed to evaluate the role of three-dimensional (3D) echocardiography in this respect. METHODS AND RESULTS: Seventy-five patients were studied prior to mitral valve repair surgery. A scoring protocol was devised for recognition of the eight Carpentier segments (0=inadequate for analysis, 1=adequate, 2=good). Using surgical findings as the gold standard, TOE and 3D were compared for adequate recognition scores and accurate detection of functional morphology. Adequate recognition was more frequently obtained with 3D imaging (97% of segments by 3D c.f. 90% by TOE; p = 0.000). The major difference was seen at the commissures (adequate scores in 143/150 commissures by 3D c.f. 90/150 by TOE; p = 0.000). 3D matched more closely to surgical findings, achieving exact functional description in 92% of segments vs 79% segments with TOE (p = 0.000). This incremental value of 3D was seen in both commissures and the anterior leaflet but not in the posterior leaflet. CONCLUSIONS: In this study 3D was superior not only for complete recognition of the mitral valve but also for the accurate localisation and identification of pathology.