Calvin Woon-Loong Chin

Cardiovascular magnetic resonance reference ranges for the heart and aorta in Chinese at 3T.

BackgroundCardiovascular magnetic resonance (CMR) reference ranges have not been well established in Chinese. Here we determined normal cardiac and aortic reference ranges in healthy Singaporean Chinese and investigated how these data might affect clinical interpretation of CMR scans.MethodsIn 180 healthy Singaporean Chinese (20 to 69xa0years old; males, nu2009=u200991), comprehensive cardiac assessment was performed using the steady state free precision technique (3T Ingenia, Philips) and images were analysed by two independent observers (CMR42, Circle Cardiovascular Imaging). Measurements were internally validated using standardized approaches: left ventricular mass (LVM) was measured in diastole and systole (with and without papillary muscles) and stroke volumes were compared in both ventricles. All reference ranges were stratified by sex and age; and “indeterminate/borderline” regions were defined statistically at the limits of the normal reference ranges. Results were compared with clinical measurements reported in the same individuals.ResultsLVM was equivalent in both phases (mean difference 3.0u2009±u20092.5xa0g; Pu2009=u20090.22) and stroke volumes were not significantly different in the left and right ventricles (Pu2009=u20090.91). Compared to females, males had larger left and right ventricular volumes (Pu2009<u20090.001 for all). Indexed LVM was significantly higher in males compared to females (50u2009±u20097 versus 38u2009±u20095xa0g/m2, respectively; Pu2009<u20090.001). Overall, papillary muscles accounted for only ~2xa0% of the total LVM. Indexed atrial sizes and aortic root dimensions were similar between males and females (Pu2009>u20090.05 for all measures). In both sexes, age correlated negatively with left and right ventricular volumes; and positively with aortic sinus and sinotubular junction diameters (Pu2009<u20090.0001 for all). There was excellent agreement in indexed stroke volumes in the left and right ventricles (0.1±5.7mL/m2, 0.7±6.2 mL/m2, respectively), LVM (0.6±6.4g/m2), atrial sizes and aortic root dimensions between values reported in clinical reports and our measured reference ranges.ConclusionsComprehensive sex and age-corrected CMR reference ranges at 3T have been established in Singaporean Chinese. This is an important step for clinical practice and research studies of the heart and aorta in Asia.

Endothelial function is associated with myocardial diastolic function in women with systemic lupus erythematosus

Endothelial dysfunction is associated with traditional and systemic lupus erythematosus (SLE)-specific risk factors, and early data suggest reversibility of endothelial dysfunction with therapy. The clinical relevance of endothelial function assessment has been limited by the lack of studies, demonstrating its prognostic significance and impact on early myocardial function. Therefore, we aimed to determine the association between endothelial and myocardial diastolic function in SLE women. Women with SLE and no coronary artery disease were prospectively recruited and underwent radionuclide myocardial perfusion imaging (MPI) (Jetstream, Philips, the Netherlands) to exclude subclinical myocardial ischemia. Cardiac and vascular functions were assessed in all patients (Alpha 10, Aloka, Tokyo). Diastolic function was assessed using pulse wave early (E) and late mitral blood inflow and myocardial tissue Doppler (mean of medial and lateral annulus e′) velocities. Endothelial function was measured using brachial artery flow-mediated vasodilatation (FMD%). Univariate and multivariate linear regressions were used to assess the association between FMD% and myocardial diastolic function, adjusting for potential confounders. Thirty-eight patients without detectable myocardial ischemia on MPI were studied (mean age 44xa0±xa010xa0years; mean disease duration 14xa0±xa06xa0years). About 61xa0% of patients had normal diastolic function (E/e′ ≤xa08), and 5xa0% of patients had definite diastolic dysfunction with E/e′ >xa013 (mean 7.1xa0±xa02.9). FMD% was associated with E/e′ (regression coefficient βxa0=xa0−0.35; 95xa0% CIxa0−0.62 to −0.08; pxa0=xa00.01) independent of systolic blood pressure, age, and SLICC/ACR Damage Index.

Assessing exercise cardiac reserve using real-time cardiovascular magnetic resonance

BackgroundExercise cardiovascular magnetic resonance (ExCMR) has great potential for clinical use but its development has been limited by a lack of compatible equipment and robust real-time imaging techniques. We developed an exCMR protocol using an in-scanner cycle ergometer and assessed its performance in differentiating athletes from non-athletes.MethodsFree-breathing real-time CMR (1.5T Aera, Siemens) was performed in 11 athletes (5 males; median age 29 [IQR: 28–39] years) and 16 age- and sex-matched healthy volunteers (7 males; median age 26 [interquartile range (IQR): 25–33] years). All participants underwent an in-scanner exercise protocol on a CMR compatible cycle ergometer (Lode BV, the Netherlands), with an initial workload of 25W followed by 25W-increment every minute. In 20 individuals, exercise capacity was also evaluated by cardiopulmonary exercise test (CPET). Scan-rescan reproducibility was assessed in 10 individuals, at least 7 days apart.ResultsThe exCMR protocol demonstrated excellent scan-rescan (cardiac index (CI): 0.2 ± 0.5L/min/m2) and inter-observer (ventricular volumes: 1.2 ± 5.3mL) reproducibility. CI derived from exCMR and CPET had excellent correlation (r = 0.83, p < 0.001) and agreement (1.7 ± 1.8L/min/m2). Despite similar values at rest (P = 0.87), athletes had increased exercise CI compared to healthy individuals (at peak exercise: 12.2 [IQR: 10.2–13.5] L/min/m2 versus 8.9 [IQR: 7.5–10.1] L/min/m2, respectively; P < 0.001). Peak exercise CI, where image acquisition lasted 13–17 s, outperformed that at rest (c-statistics = 0.95 [95% confidence interval: 0.87–1.00] versus 0.48 [95% confidence interval: 0.23–0.72], respectively; P < 0.0001 for comparison) in differentiating athletes from healthy volunteers; and had similar performance as VO2max (c-statistics = 0.84 [95% confidence interval = 0.62–1.00]; P = 0.29 for comparison).ConclusionsWe have developed a novel in-scanner exCMR protocol using real-time CMR that is highly reproducible. It may now be developed for clinical use for physiological studies of the heart and circulation.

The role of cardiac biochemical markers in aortic stenosis

Abstract Calcified aortic stenosis is one of the most common causes of heart failure in the elderly. Current guidelines recommend aortic valve replacement in patients with severe disease and evidence of decompensation based on either symptoms or impaired systolic ejection fraction. However, symptoms are often subjective whilst impaired ejection fraction is not a sensitive marker of ventricular decompensation. Interest has surrounded the use of cardiac biochemical markers as objective measures of left ventricular decompensation in aortic stenosis. We will first examine mechanisms of release of biochemical markers associated with myocardial wall stress (BNP/NT-proBNP), myocardial fibrosis (markers of collagen metabolism, galectin-3, soluble ST2) and myocyte death/myocardial ischemia (high-sensitivity cardiac troponins, heart-type fatty acid binding protein, myosin-binding protein C); and discuss future directions of these markers.

Beyond fitness tracking: The use of consumer-grade wearable data from normal volunteers in cardiovascular and lipidomics research

The use of consumer-grade wearables for purposes beyond fitness tracking has not been comprehensively explored. We generated and analyzed multidimensional data from 233 normal volunteers, integrating wearable data, lifestyle questionnaires, cardiac imaging, sphingolipid profiling, and multiple clinical-grade cardiovascular and metabolic disease markers. We show that subjects can be stratified into distinct clusters based on daily activity patterns and that these clusters are marked by distinct demographic and behavioral patterns. While resting heart rates (RHRs) performed better than step counts in being associated with cardiovascular and metabolic disease markers, step counts identified relationships between physical activity and cardiac remodeling, suggesting that wearable data may play a role in reducing overdiagnosis of cardiac hypertrophy or dilatation in active individuals. Wearable-derived activity levels can be used to identify known and novel activity-modulated sphingolipids that are in turn associated with insulin sensitivity. Our findings demonstrate the potential for wearables in biomedical research and personalized health.

Stress cardiovascular magnetic resonance imaging: current and future perspectives

ABSTRACT Introduction: Vasodilator and dobutamine are the main pharmacological agents used in current stress cardiovascular magnetic resonance (CMR). Exercise stress has well-established advantages and it is commonly used in other stress imaging, but the technical considerations have limited its use in stress CMR. In this review, we will describe the diagnostic performance, prognostic value, strengths and challenges of current stress CMR techniques. We will also discuss future perspectives of exercise stress CMR. Areas covered: Despite notable mechanistic differences, vasodilator and dobutamine stress CMR offer similar diagnostic and prognostic value in coronary artery disease. Combined perfusion and wall motion assessment has been explored with dobutamine stress CMR: diagnostic sensitivity improved at the expense of reduced specificity. However, a combined assessment may provide additional prognostic value in selected patients. There is emerging interest and promising data in exercise stress CMR because of the availability of CMR-compatible stress equipment and development of novel real-time sequences that allow imaging during exercise with adequate spatiotemporal resolution. Expert commentary: Exercise stress CMR is able to assess wall motion abnormalities, perfusion defects, exercise capacity and viability in a single examination. This holds important clinical potential in a variety of cardiovascular conditions.

Cardiac magnetic resonance T1 and extracellular volume mapping with motion correction and co-registration based on fast elastic image registration

ObjectiveOur aim was to investigate the technical feasibility of a novel motion compensation method for cardiac magntic resonance (MR) T1 and extracellular volume fraction (ECV) mapping.Materials and methodsNative and post-contrast T1 maps were obtained using modified look-locker inversion recovery (MOLLI) pulse sequences with acquisition scheme defined in seconds. A nonrigid, nonparametric, fast elastic registration method was applied to generate motion-corrected T1 maps and subsequently ECV maps. Qualitative rating was performed based on T1 fitting-error maps and overlay images. Local deformation vector fields were produced for quantitative assessment. Intra- and inter-observer reproducibility were compared with and without motion compensation.ResultsEighty-two T1 and 39 ECV maps were obtained in 21 patients with diverse myocardial diseases. Approximately 60% demonstrated clear quality improvement after motion correction for T1 mapping, particularly for the poor-rating cases (23% before vs 2% after). Approximately 67% showed further improvement with co-registration in ECV mapping. Although T1 and ECV values were not clinically significantly different before and after motion compensation, there was improved intra- and inter-observer reproducibility after motion compensation.ConclusionsAutomated motion correction and co-registration improved the qualitative assessment and reproducibility of cardiac MR T1 and ECV measurements, allowing for more reliable ECV mapping.

Inter-relationship between ageing, body mass index, diabetes, systemic blood pressure and intraocular pressure in Asians: 6-year longitudinal study

Background To investigate the biological effect of ageing on intraocular pressure (IOP) and risk factors in a population-based cohort study of Malay and Indian adults. Methods Participants aged 40–80 years were recruited for baseline and 6-year follow-up visits between 2004–2009 and 2010–2015, respectively. Blood pressure (BP) was measured with an automatic BP monitor and IOP were obtained by Goldmann applanation tonometry. Main outcome was change in IOP, defined as the difference between the 6-year IOP and the baseline IOP. Linear regression models were used to investigate the association of changes in IOP with risk factors. Results Participants without a history of glaucoma or cataract surgery at baseline were included (n = 3188; mean age: 54±9 years) . Their average IOP was reduced (−0.5±3.1u2009mm Hg), except for those who developed hypertension at follow-up (0.0±3.1u2009mm Hg). After adjusting for covariates, changes in IOP were negatively associated with age (β=−0.07, 95%u2009CI −0.13 to −0.01) and positively associated with body mass index, diabetes, hypertension (normotensive as reference group; newly developed hypertensive (β=0.67, 95%u2009CI 0.39 to 0.95) and chronic hypertensive (β=0.46, 95%u2009CI 0.22 to 0.70)), baseline systolic BP (SBP) (β=0.20, 95%u2009CI 0.14 to 0.26) and diastolic BP (DBP) (β=0.33, 95%u2009CI 0.22 to 0.44), as well as with 6-year increases in SBP (β=0.27, 95%u2009CI 0.21 to 0.33) and DBP (β=0.52, 95%u2009CI 0.41 to 0.63). Conclusions Normal ageing and reduced systemic BP are associated with reduced IOP in Malay and Indian adults. Given that high IOP is a risk factor for glaucoma, our finding highlights the importance of controlling hypertension in older adults, where hypertension and glaucoma incidences are on a rise.

Fractal analysis of left ventricular trabeculations is associated with impaired myocardial deformation in healthy Chinese

BackgroundLeft ventricular (LV) non-compaction (LVNC) is defined by extreme LV trabeculation, but is measured variably. Here we examined the relationship between quantitative measurement in LV trabeculation and myocardial deformation in health and disease and determined the clinical utility of semi-automated assessment of LV trabeculations.MethodsCardiovascular magnetic resonance (CMR) was performed in 180 healthy Singaporean Chinese (age 20–69xa0years; males, nu2009=u200991), using balanced steady state free precession cine imaging at 3T. The degree of LV trabeculation was assessed by fractal dimension (FD) as a robust measure of trabeculation complexity using a semi-automated technique. FD measures were determined in healthy men and women to derive normal reference ranges. Myocardial deformation was evaluated using feature tracking. We tested the utility of this algorithm and the normal ranges in 10 individuals with confirmed LVNC (non-compacted/compacted; NC/C ratiou2009>u20092.3 and ≥1 risk factor for LVNC) and 13 individuals with suspected disease (NC/C ratiou2009>u20092.3).ResultsFractal analysis is a reproducible means of assessing LV trabeculation extent (intra-class correlation coefficient: intra-observer, 0.924, 95% CI [0.761–0.973]; inter-observer, 0.925, 95% CI [0.821–0.970]). The overall extent of LV trabeculation (global FD: 1.205u2009±u20090.031) was independently associated with increased indexed LV end-diastolic volume and mass (sβxa0=u20090.35; pu2009<u20090.001 and sβxa0=u20090.13; pu2009<u20090.01, respectively) after adjusting for age, sex and body mass index. Increased LV trabeculation was independently associated with reduced global circumferential strain (sβxa0=u20090.17, pu2009=u20090.013) and global diastolic circumferential and radial strain rates (sβxa0=u20090.25, pu2009<u20090.001 and sβxa0=u2009−0.15, pu2009=u20090.049, respectively). Abnormally high FD was observed in all patients with a confirmed diagnosis of LVNC. Five out of 13 individuals with suspected LVNC had normal FD, despite NC/Cu2009>u20092.3.ConclusionThis study defines the normal range of LV trabeculation in healthy Chinese that can be used to make or refute a diagnosis of LVNC using the fractal analysis tool, which we make freely available. We also show that increased myocardial trabeculation is associated with higher LV volumes, mass and reduced myocardial strain.

Disparity Between Indications for and Utilization of Implantable Cardioverter Defibrillators in Asian Patients With Heart Failure

Background— Implantable cardioverter defibrillators (ICDs) are lifesaving devices for patients with heart failure (HF) and reduced ejection fraction. However, utilization and determinants of ICD insertion in Asia are poorly defined. We determined the utilization, associations of ICD uptake, patient-perceived barriers to device therapy and, impact of ICDs on mortality in Asian patients with HF. Methods and Results— Using the prospective ASIAN-HF (Asian Sudden Cardiac Death in Heart Failure) registry, 5276 patients with symptomatic HF and reduced ejection fraction (HFrEF) from 11 Asian regions and across 3 income regions (high: Hong Kong, Japan, Korea, Singapore, and Taiwan; middle: China, Malaysia, and Thailand; and low: India, Indonesia, and Philippines) were studied. ICD utilization, clinical characteristics, as well as device perception and knowledge, were assessed at baseline among ICD-eligible patients (EF ⩽35% and New York Heart Association Class II-III). Patients were followed for the primary outcome of all-cause mortality. Among 3240 ICD-eligible patients (mean age 58.9±12.9 years, 79.1% men), 389 (12%) were ICD recipients. Utilization varied across Asia (from 1.5% in Indonesia to 52.5% in Japan) with a trend toward greater uptake in regions with government reimbursement for ICDs and lower out-of-pocket healthcare expenditure. ICD (versus non-ICD) recipients were more likely to be older (63±11 versus 58±13 year; P<0.001), have tertiary (versus ⩽primary) education (34.9% versus 18.1%; P<0.001) and be residing in a high (versus low) income region (64.5% versus 36.5%; P<0.001). Among 2000 ICD nonrecipients surveyed, 55% were either unaware of the benefits of, or needed more information on, device therapy. ICD implantation reduced risks of all-cause mortality (hazard ratio, 0.71; 95% confidence interval, 0.52–0.97) and sudden cardiac deaths (hazard ratio, 0.33; 95% confidence interval, 0.14–0.79) over a median follow-up of 417 days. Conclusions— ICDs reduce mortality risk, yet utilization in Asia is low; with disparity across geographic regions and socioeconomic status. Better patient education and targeted healthcare reforms in extending ICD reimbursement may improve access. Clinical Trial Registration— URL: https://clinicaltrials.gov/ct2/show/NCT01633398. Unique identifier: NCT01633398.