EY1920 Year Book

71 70 Fung Sau Yung Study Title: Cardiovascular Magnetic Resonance (CMR) Imaging for Assessment of Heart Failure with Preserved Ejection Fraction (HFpEF) Background and Objectives § Heart failure with preserved ejection fraction (HFpEF) despite being widely prevalent, remains challenging in diagnosis. Currently, echocardiography is the main diagnostic tool, but there are no other non-invasive alternatives. § Since the major pathological hallmark of HFpEF is reported to be diffuse interstitial fibrosis, that leads to diastolic dysfunction in this disease entity. This study therefore aims to evaluate the diagnostic potential of several novel CMR parameters, namely T1 mapping and extracellular volume (ECV) fraction, in terms of their utility in quantification and characterization of myocardial tissue for diagnosis of HFpEF. Methods § This is a prospective case-control study with 3 cohorts of subjects (16 HFpEF, 23 indeterminate, 24 normal volunteers) who had all undergone blood test (NT- proBNP), echocardiogram, CMR assessment, (optional) invasive catherization within a 24-hour time span. § Categorization of HFpEF cohort was based on the European Society of Cardiology (ESC) guidelines, which refers to complete fulfillment of the following 4 criteria: 1. Signs and symptoms of heart failure; 2. Normal or preserved left ventricular ejection fraction (i.e. LVEF≥50%); 3. Elevated levels of natriuretic peptides 4. Echocardiographic findings of at least one of the following: either left ventricular hypertrophy (LVH) or left atrial enlargement (LAE); or diastolic dysfunction as evident from echocardiographically derived measurements § Normal volunteers had no cardiac symptoms or signs, absence of cardiovascular risk factors and disease. § Image acquisition: All CMR images were acquired on a 3T Philips Achieva scanner. § Image analysis: All post-processings were done on CVI42 software (Circle Cardiovascular Imaging, Calgary, Alberta, Canada, version 10.13.6) § Statistical analysis: Analysis was carried out with SPSS IBM statistics, version 26. A p-value of < 0.05 was used to determine statistical significance. i. For continuous variables: Shapiro-wilk test (normality), ANOVA test, Kruskal-Wallis test, T-test, Mann-Whitney U test ii. For categorial variables: chi-square test iii. Receiver operator characteristic (ROC) analysis were used to determine diagnostic power in terms of AUC, sensitivity and specificity Results § Exact figures of baseline characteristics and research parameters indices are shown in Table 1. § Receiver operator characteristic (ROC) analysis was done on parameters as shown in Figure 1. Parameter AUC Cut-offs Sensitivity Specificity p-value Native T1 (ms) 0.833 1271.45 75% 81.2% <0.001 ECV (%) 0.799 26.65 62.5% 93.7% 0.001 Healthy (n=16) Indeterminate (n=23) HFpEF (n=24) p- value General Information Age (years) #^ 57.69 ± 4.38 # *70.43 ± 8.55 * ^ 77.79 ± 8.23 <0.001 Male 7 (43.8) 11 (47.8) 10 (41.7) 0.912 Body surface area (m 2 ) 1.66 ± 0.22 1.75 ± 0.20 1.66 ± 0.21 0.310 Systolic Blood Pressure (mmHg) ^ 132.4414.1 3 145.57 ± 24.75 ^ 145.82 ± 23.26 0.073 Diastolic Blood Pressure (mmHg) 81.69 ± 7.95 77.64 ± 13.40 76.59 ± 14.84 0.461 Pulse rate (per minute) 72.63 ± 15.90 77.65 ± 14.95 75.18 ± 12.73 0.339 NT-proBNP NT-proBNP (pg/ml) #^ 31.36 (5.00-33.26) # *66.06 (35.35- 114.50) * ^ 546.40 (211.45- 1622.20) <0.001 CMR Parameters LV end-diastolic volume index (mL/m 2 ) 72.35 ± 16.85 72.59 ± 10.48 77.87 ± 17.82 0.580 LV end-systolic volume index (mL/m 2 ) 28.95 ± 8.79 *27.10 ± 5.48 *34.20 ± 12.83 0.137 LV ejection fraction (%) 60.22 ± 6.26 *62.72 ± 5.44 *57.10 ± 7.77 0.019 LV mass index (g/m 2 ) #^ 41.92 ± 9.30 # 50.68 ± 8.17 ^ 51.27 ± 13.68 0.006 LA volume index (mL/m 2 ) ^ 41.80 ± 7.98 *45.00 ± 12.33 * ^ 80.19 ± 51.56 <0.001 Late gadolinium enhancement 0 (0) *0 (0) *4 (16.7) 0.031 CMR Research Parameters Native T1 times of myocardium (ms) ^1246.37 ± 32.15 *1269.81 ± 42.75 *^1308.09 ± 57.20 0.001 ECV (extracellular volume) fraction (%) ^24.13 ± 2.22 *25.52 ± 2.79 *^28.22 ± 5.16 0.003 T2 mapping (ms) ^46.99 ± 1.70 *49.43 ± 3.50 *^54.08 ± 9.97 0.011 Pulse Wave Velocity (m/ms) 12.15 ± 5.41 13.60 ± 7.78 20.30 ± 17.37 0.122 § Novel CMR parameters, i.e. native T1 mapping and extracellular volume fraction, have shown favorable diagnostic potential for classification of HFpEF subjects. § But in the practical context, translation of research parameters for clinical use would require further standardization in technical components. § It is also hoped that that native T1 and ECV could be used for development of risk score system dedicated to assessment of non-invasive diastolic dysfunction. Conclusion MBBS Enrichment Year 2019/20 Fung Sau Yung Full Year < RA - Cardiovascular Magnetic Resonance (CMR) Imaging for Assessment of Heart Failure with Preserved Ejection Fraction (HFpEF) at Department of Diagnostic Radiology, HKU, Hong Kong > Short-term high-fat diet exacerbates postoperative pain in an inflammation-independent manner Background: Relationship between high-fat diet (HFD) and postoperative pain has been reported, 1,2 but mechanisms remain unclear. Effects of diet per se have also been implied. 1 Methods: C57BL/6J mice are used. A hindpaw incision model is used. 3 An 5mm long incision through skin and underlying muscle is made 2mm from the heel towards the toes. Mechanical (Von Frey) and thermal (Hargreaves) sensitivity tests are carried out. Mice are sacrificed and spinal cords are harvested.. Objectives: 1. To investigate whether HFD affects thermal nociception 2. To screen for biomarkers that respond to HFD 3. To test the hypothesis that HFD-induced effects are inflammatory in nature References : 1. Song, Z., et al. (2018). "High-fat diet exacerbates postoperative pain and inflammation in a sex-dependent manner." Pain 159(9): 1731-1741. 2. Guillemot-Legris, O., et al. (2018). "Post-operative pain in mice is prolonged by diet-induced obesity and rescued by dietary intervention." Brain Behav Immun 74 : 96-105. 3. Pogatzki, Esther M. M. D. and Srinivasa N. M. D. Raja (2003). "A Mouse Model of Incisional Pain." Anesthesiology 99 (4): 1023- 1027. NC+Inc HFD+Sham HFD+Inc NC+Sham 0 2 4 6 CCL2 FC HFD+Inc NC+Inc EAAT2 GAPDH * High fat diet has dose-dependently prolonged postoperative pain. However, it does not dose-dependently worsen postoperative pain. Both 2 weeks and 4 weeks of high fat diet intensify postoperative to a similar degree. For the first time relationship between HFD and thermal nociception in the postoperative pain model is shown. However, the pro-inflammatory cytokines in the ipsilateral spinal cord (harvested at post-op D7) are the same among the 4 groups, suggesting the effects of short- term HFD are probably mediated by peripheral mechanisms. A marker of synapse function, EAAT2, is downregulated by HFD. At the same time, Iba-1 positive cell count increased. HFD either inhibits astrocyte activation during incision, or impairs synaptic glutamate metabolism. On the other hand, aftern incision HFD increased microglia proliferation. Therefore, central sensitization mechanism does play a role in HFD-induced hyperalgesia, albeit not inflammatory in nature. Results : DAPI/ Iba1 Conclusion: - HFD causes both mechanical and thermal hyperalgesia in a postoperative pain model. - 3 weeks of HFD do not alter the cytokine signature in the spinal cord, regardless of surgery treatment. - HFD rapidly downregulates EAAT2 and stimulates microglial proliferation in the CNS, which might contribute to the amplification of postoperative pain by HFD. HFD+Inc NC+Inc MBBS Enrichment Year 2019/20 Gu Kwan Yin Full Year < IC - M R e s( Me d) at HK U, H o ng K o ng > Gu Kwan Yin