Assessment and risk prediction in patients with aortic stenosis: insights from cardiovascular magnetic resonance

BACKGROUND Aortic stenosis affects not only the valve but also the myocardium. In response to the increased afterload, left ventricular hypertrophy initially occurs as a compensatory response to maintain wall stress and cardiac output but ultimately, decompensation and heart failure ensues. The transition from adaptation to decompensation is driven by myocyte death and myocardial fibrosis. The aims of the thesis are to investigate cardiovascular magnetic resonance assessment of disease severity and myocardial fibrosis, and explore its relationship with other biomarkers of disease activity and clinical outcome in patients with aortic stenosis. METHODS AND RESULTS The conventional assessment of aortic stenosis relies heavily on two-dimensional and Doppler echocardiography but there are inherent limitations in echocardiography that can affect the severity classification. I demonstrated that cardiovascular magnetic resonance offered a more accurate estimation of left ventricular volumes and mass, and excellent myocardial characterization. Indeed, inaccurate stroke volume estimation by Doppler echocardiography and inconsistent thresholds in current guidelines accounted for more than 40% of patients with discordant small-area, lowgradient aortic stenosis. These data may explain the variable prognosis reported in this unique group of patients, and argue for more accurate assessment of borderline cases with cardiovascular magnetic resonance. Late gadolinium enhancement imaging detects focal areas of established myocardial fibrosis. In many conditions, including aortic stenosis, a more diffuse form of fibrosis predominates, which is potentially reversible and not readily identified by late gadolinium enhancement. Recently several myocardial T1 mapping approaches have been developed to quantify diffuse fibrosis. Using a standardized and systematic approach, I compared several commonly used T1 mapping techniques and identified that extracellular volume had the best profile (reproducibility and discriminatory potential) for the identification of diffuse fibrosis in patients with aortic stenosis. Cardiac troponin is a structural protein present in the cardiac myocytes. Recent advances in assay technology have substantially improved sensitivity, allowing quantification of troponin concentrations with a high degree of precision in everyone. In more than 250 patients with aortic stenosis, I demonstrated that cardiac troponin I concentrations were independently associated with markers of left ventricular decompensation (hypertrophy and fibrosis) and predicted clinical outcome in patients with aortic stenosis. This suggests that myocardial fibrosis detected by cardiovascular magnetic resonance is consequent on myocardial injury secondary to left ventricular decompensation. Left ventricular hypertrophy with strain pattern on a 12-lead electrocardiogram is associated with poor outcome in patients with aortic stenosis, but the mechanism of this electrocardiographic pattern has not been described. In more than 300 patients with aortic stenosis, I demonstrated that these characteristic repolarization abnormalities were a highly specific marker of focal mid-wall myocardial fibrosis (specificity of 99% and sensitivity of 54%). Moreover, the prognostic value of this electrocardiographic pattern was again confirmed with markedly worse long-term outcomes in these patients. CONCLUSION I have demonstrated that cardiovascular magnetic resonance can assist in the assessment of disease severity in patients with aortic stenosis and discordant echocardiographic findings. Moreover, I have validated the assessment of diffuse myocardial fibrosis, as well as, demonstrated the close association between myocardial fibrosis and biomarkers of myocardial injury and electrocardiographic strain pattern that predicted an adverse outcome in patients with aortic stenosis

A Systematic Quality Scoring Analysis to Assess Automated Cardiovascular Magnetic Resonance Segmentation Algorithms

BACKGROUND: The quantitative measures used to assess the performance of automated methods often do not reflect the clinical acceptability of contouring. A quality-based assessment of automated cardiac magnetic resonance (CMR) segmentation more relevant to clinical practice is therefore needed. OBJECTIVE: We propose a new method for assessing the quality of machine learning (ML) outputs. We evaluate the clinical utility of the proposed method as it is employed to systematically analyse the quality of an automated contouring algorithm. METHODS: A dataset of short-axis (SAX) cine CMR images from a clinically heterogeneous population (n = 217) were manually contoured by a team of experienced investigators. On the same images we derived automated contours using a ML algorithm. A contour quality scoring application randomly presented manual and automated contours to four blinded clinicians, who were asked to assign a quality score from a predefined rubric. Firstly, we analyzed the distribution of quality scores between the two contouring methods across all clinicians. Secondly, we analyzed the interobserver reliability between the raters. Finally, we examined whether there was a variation in scores based on the type of contour, SAX slice level, and underlying disease. RESULTS: The overall distribution of scores between the two methods was significantly different, with automated contours scoring better than the manual (OR (95% CI) = 1.17 (1.07–1.28), p = 0.001; n = 9401). There was substantial scoring agreement between raters for each contouring method independently, albeit it was significantly better for automated segmentation (automated: AC2 = 0.940, 95% CI, 0.937–0.943 vs manual: AC2 = 0.934, 95% CI, 0.931–0.937; p = 0.006). Next, the analysis of quality scores based on different factors was performed. Our approach helped identify trends patterns of lower segmentation quality as observed for left ventricle epicardial and basal contours with both methods. Similarly, significant differences in quality between the two methods were also found in dilated cardiomyopathy and hypertension. CONCLUSIONS: Our results confirm the ability of our systematic scoring analysis to determine the clinical acceptability of automated contours. This approach focused on the contours' clinical utility could ultimately improve clinicians' confidence in artificial intelligence and its acceptability in the clinical workflo

The ARIC predictive model reliably predicted risk of type II diabetes in Asian populations

10.1186/1471-2288-12-48BMC Medical Research Methodology12

The Application of Optical Coherence Tomography Angiography in Systemic Hypertension: A Meta-Analysis

10.3389/fmed.2021.778330Frontiers in Medicine877833

Impact of hypertension on retinal capillary microvasculature using optical coherence tomographic angiography

Objective: Reduction in capillary density or rarefaction is a hallmark of essential hypertension. We measured the retinal capillary density using noninvasive optical coherence tomographic angiography (OCT-A) in adults with treated systemic hypertension and determined possible correlations with ambulatory blood pressure (BP) and renal parameters. Methods: This observational cross-sectional study consisted of 153 normal eyes from 77 nondiabetic hypertensive adults [mean (SD) age, 58 (9) years; 49% women; 23% poorly controlled BP]. Data on 24-h ambulatory BP monitoring, serum creatinine, and urine microalbumin/creatinine ratio (MCR) were collected. Estimated glomerular filtration rate (eGFR) was calculated based on CKD-EPI Creatinine Equation. Retinal capillary density measured with the OCT-A (AngioVue) at superficial (SVP) and deep vascular plexuses (DVP). Linear regression was used to investigate the association of risk factors with capillary density. Results: Retinal capillary density (percentage) at DVP was reduced in patients with poorly controlled BP (SBP = 148 ± 8 mmHg; 27.2 ± 13.0) compared with those with well controlled BP (SBP = 125 ± 9 mmHg; 34.7 ± 11.3). In the multivariable analysis, poorly controlled BP [β = −6.49, 95% confidence interval (CI), −12.39 to −0.59], higher SBP (β = −0.23, 95% CI −0.44 to −0.02) and lower eGFR (β = 6.42, 95% CI 1.25–11.60) were associated with sparser retinal capillary density. Systemic factors were not associated with capillary density at SVP (all P > 0.05). Conclusion: In adults with treated systemic hypertension, retinal capillary density reduced with higher BP and poorer eGFR. These findings highlight the potential role of OCT-A to study early microvascular changes because of systemic hypertension.National Medical Research Council (NMRC)Published versionL.S.Funding received for this workfrom National Medical Research Council (NMRC/CG/C010A/2017), Singapore

Impact of systemic vascular risk factors on the choriocapillaris using optical coherence tomography angiography in patients with systemic hypertension

Abstract We investigated the characteristics of the choriocapillaris flow voids using optical coherence tomography angiography (OCTA) in 85 patients (164 eyes) with hypertension (mean ± SD age, 56 ± 11 years; 45% women; 20% poorly controlled BP; 16% diabetes) who are without ocular diseases and determined possible correlations with systemic vascular risk factors. Data on 24-hour ambulatory blood pressure (BP), serum creatinine, and urine microalbumin/creatinine ratio (MCR) were collected. Estimated glomerular filtration rate (eGFR) was calculated based on CKD-EPI Creatinine Equation. OCTA imaging (6 × 6 mm scans; AngioVue) with quantitative microvascular analysis of the choriocapillaris was performed. Linear regression was used to investigate the association of systemic risk factors with area (percentage), size (pixels) and number of choriocapillaris flow voids. Diabetes (β = 0.33; 95% CI, 0.02 to 0.63) and daytime systolic BP (β = −0.13; 95% CI, −0.24 to −0.02) were associated with areas of flow voids. Age (β = 0.21; 95% CI, 0.06 to 0.36) and daytime diastolic BP (β = −0.18; 95% CI, −0.34 to −0.02) were associated with size of flow voids. Age (β = −21.21; 95% CI, −31.79 to −10.63) and nighttime diastolic BP (β = 13.89; 95% CI, 0.61 to 27.17) were associated with number of flow voids. Kidney parameters were not associated with any features of flow voids. In patients with hypertension, a higher BP appeared to increase blood flow in the choriocapillaris which needs to be considered when using the OCTA to study eye diseases in hypertensives