Preoperative Right Ventricular Free-Wall Longitudinal Strain as a Prognosticator in Isolated Surgery for Severe Functional Tricuspid Regurgitation

Background Severe tricuspid regurgitation (TR) should be intervened before the development of irreversible right ventricular (RV) dysfunction. However, current guidelines do not provide criterion related to RV systolic function to guide optimal surgical timing. We investigated the prognostic value of RV longitudinal strain in patients undergoing isolated surgery for severe functional TR. Methods and Results We enrolled 115 consecutive patients (aged 62±10 years; 23.5% men; 62.6% [n=72] with previous left-sided valve surgery) who underwent isolated surgery for severe functional TR at 2 tertiary centers. Preoperative clinical and echocardiographic parameters, including RV free-wall longitudinal strain (RVFWSL), were collected. The primary end point was a composite of cardiac death and unplanned readmission attributable to cardiovascular causes 5 years after surgery. Forty patients (34.8%) reached the primary end point during 333 person-years of follow-up. There were 11 cardiac deaths and 34 unplanned readmissions attributable to cardiovascular causes, with 5 patients experiencing both. An absolute preoperative RVFWSL <24% was associated with the primary end point (hazard ratio, 2.30; 95% CI, 1.22-4.36; P=0.011), independent of clinical risk factors, including European System for Cardiac Operative Risk Evaluation II and hemoglobin levels. Meanwhile, other conventional echocardiographic measures of RV systolic function were not significant. The addition of an absolute RVFWSL <24% provided incremental prognostic value to the clinical model for predicting the primary end point. Conclusions Preoperative RVFWSL as an indicator of RV dysfunction was an independent prognosticator in patients undergoing isolated surgery for severe functional TR. Thus, preoperative RVFWSL could help determine the optimal surgical timing for severe functional TR.ope

Association between arterial stiffness and left ventricular diastolic function: A large population-based cross-sectional study

Background: The association between arterial stiffness and left ventricular (LV) diastolic function has been demonstrated in several studies, but the samples size in those studies was small. This study aims to verify this issue in a large number of study subjects. Methods: A total of 7,013 consecutive participants (mean age 60.6 years and 43.3% female) who underwent both baPWV and transthoracic echocardiography were retrospectively analyzed. Subjects with significant cardiac structural abnormalities were excluded. Results: There were significant correlations of baPWV with septal e' velocity (r = - 0.408; P 2.8 m/s (OR, 1.60; 95% CI, 1.23-2.09; P < 0.001) but not with LAVI ≥ 34 mL/m2 (OR, 0.89; 95% CI, 0.76-1.03; P = 0.123). Conclusions: Increased arterial stiffness, as measured by baPWV, was associated with abnormal diastolic function parameters in a large number of study participants, providing strong evidence to the existing data about ventricular-vascular coupling.ope

Sex differences in the prognosis of patients with hypertrophic cardiomyopathy

We investigated sex-related differences in the prognosis of patients with hypertrophic cardiomyopathy (HCM) using the Korea National Health Insurance Service database. From 2010 to 2016, 9524 patients diagnosed with HCM and had more than 1-year follow-up period were analyzed. The primary endpoint was the composite of cardiovascular death or new-onset heart failure (HF) admission. Propensity score-matching analysis was performed to adjust for different baseline characteristics. With a 4.4-years' median follow-up interval (range 2.0-6.6 years) and male predominance (77.6%), women with HCM were older (52.6 ± 9.7 vs. 51.4 ± 9.1, p < 0.001), had lower incomes, more comorbidities based on Charlson comorbidity index. Women with HCM had a higher incidence of the primary endpoint than men (incidence rate: 34.15 vs. 22.83 per 1000 person-years, log-rank p < 0.001). Multivariable Cox analysis showed that female sex was a poor prognostic factor for the primary endpoint (HR 1.43, 95% CI 1.24-1.64, p < 0.001). This was mainly driven by a higher incidence of new-onset HF admission (HR 1.55, 95% CI 1.34-1.80). However, there was no difference in the incidence of cardiovascular death between the sexes. This result was concordant in the propensity score-matched cohort. In conclusion, women with HCM have worse prognosis, which was mainly driven by a higher new-onset HF admission.ope

Spin dynamics of magnetic nanoparticles and its application for magnetic hyperthermia

학위논문 (박사)-- 서울대학교 대학원 : 공과대학 재료공학부, 2018. 2. 김상국, 김미영.Localized magnetic particle hyperthermia heating treatment using magnetic nanoparticles continue to be an active area of cancer research. In magnetic hyperthermia, magnetic nanoparticles are subjected in alternating magnetic field, thus forced to release energy-dissipation as a heat (via various mechanisms: Néel-Brown relaxation, hysteresis loss) in their surrounding while neighboring cancer cells undergo severe thermal shock and potential destruction. One of the critical issues of the mechanisms for describing the conventional hyperthermia treatment is relatively low heating power, which is not enough to kill cancer cells. To improve the heating performance of magnetic nanoparticles, there have been numerous researches using various analysis methods. However, since the mechanism of heat generation from magnetic nanoparticles is not newly proposed, the reported researches have limitations on the degree of improvement in heating power. Here, we have proposed a new mechanism for the energy-dissipation of magnetic nanoparticles based on resonance of collective spin dynamics that can maximize the heating power. First, we explored robust non-linear magnetization dynamics and the associated high-efficiency energy-dissipation effect in single-domain soft magnetic nanospheres, as excited by oscillating magnetic fields of different frequencies and amplitudes under given static magnetic fields. We conducted micromagnetic simulations to explore the novel magnetization dynamics of soft magnetic particles and additional analytical derivations of the energy-dissipation rate for the steady-state regime by varying the frequency and strength of rotating magnetic fields for different Gilbert damping constants and static magnetic field strengths. All of the simulation results and analytical calculations agree well quantitatively. The dynamic origin of such a high-efficiency energy-dissipation mechanism is completely different from those of the typical ones used in bio-applications. Furthermore, we have extended the object of the energy-dissipation study by the magnetic resonance phenomenon from the single-domain state to the magnetic-vortex state. Using both micromagnetic simulations and semi-analytical analysis, we addressed the similarities and differences between the single-domain state and magnetic-vortex state in terms of the temporal evolutions of the spin dynamics and energy-dissipation calculated for all variables given to the system. The energy-dissipation generated by resonant excitation of magnetic vortex was smaller than the energy-dissipation of single-domain state, and it is directly related to , where is the average magnetization component over the sphere volume in the vortex-core orientation. Finally, we identify the existence of spin-dynamics driven energy-dissipation in magnetic nanoparticles from ferromagnetic resonance experiments using vector network analyzer and compare the results with analytical calculation and micromagnetic simulation. From the experiments, we observed that the energy-dissipation released by the resonance of spins inside the nanoparticles well corresponded to the calculated results. This work provides further insights into the fundamentals of magnetization dynamics in magnetic particles and the associated energy dissipation effect, and suggests a highly efficient means of magnetic-hyperthermia-applicable energy dissipation.Chapter 1. General Introduction 1 1.1. Research Objectives 2 1.2. References 7 Chapter 2. Research Background 9 2.1. Size Dependent Properties of Magnetic Nanoparticles 9 2.1.1. Spin Configurations 9 2.1.2. Characteristic Frequencies of Magnetic Nanoparticles 11 2.2. Numerical Calculations for Spin Dynamics 18 2.2.1. Micromagnetics 18 2.2.2. Micromagnetic Simulations 25 2.3. Vector Network Analyzer (VNA) 27 2.3.1. VNA-FMR Measurement 27 2.3.2. Reflection VNA-FMR technique 27 2.3.3. Transmission VNA-FMR technique 28 2.4. Appendix 32 2.5. References 36 Chapter 3. Dynamic Origin of Highly Efficient Energy-dissipation in Soft Magnetic Nanoparticles in Single-domain State 39 3.1. Introduction 39 3.2. Modeling 41 3.3. Results and Discussion 44 3.3.1. Characteristic Dynamic Motions of Magnetization 44 3.3.2. Energy-dissipation Rate of Single-domain State 54 3.4. References 68 Chapter 4. A Study on the Physical Origin of Low Frequency and High Efficiency Energy-dissipation Due to Resonant Precession of Magnetic-vortex Core 71 4.1. Introduction 71 4.2. Modeling 75 4.3. Results and Discussion 78 4.3.1. Characteristic Dynamic Motions of Magnetic-vortex Core 78 4.3.2. Energy-Dissipation Rate of Magnetic-vortex State 81 4.3.3. Consideration on Influence of Temperature 99 4.5. References 101 Chapter 5. Measurement of Energy-dissipation Caused by Spin Dynamics 103 5.1. Introduction 103 5.2. Assumption and Validity 106 5.3. Method 111 5.3.1. Experimental Method 111 5.3.2. Analytical Calculation Method 112 5.4. Results and Discussion 115 5.5. Referecnces 120 Chapter 6. Conclusion 121 Publication List 123 Abstract (in Korean) 125Docto

Prognostic value of preoperative left ventricular global longitudinal strain for predicting postoperative myocardial injury and mortality in patients undergoing major non-cardiac surgery (SOLOMON study)

Background: The usefulness of preoperative measurement of left ventricular global longitudinal strain (LVGLS) for predicting prognosis in patients undergoing non-cardiac surgery has not been evaluated. We analyzed the prognostic value of LVGLS in predicting postoperative 30-day cardiovascular events and myocardial injury after non-cardiac surgery (MINS). Methods: This prospective cohort study was conducted in two referral hospitals and included 871 patients who underwent non-cardiac surgery <1 month after preoperative echocardiography. Those with ejection fraction <40%, valvular heart disease, and regional wall motion abnormality were excluded. The co-primary endpoints were the (1) composite incidence of all-cause death, acute coronary syndrome (ACS), and MINS and (2) com-posite incidence of all-cause death and ACS. Results: Among the 871 participants enrolled (mean age: 72.9 years; female: 60.8%), there were 43 cases of the primary endpoint (4.9%): 10 deaths, 3 ACS, and 37 MINS. Participants with impaired LVGLS (<= 16.6%) had a higher incidence of the co-primary endpoints (log-rank P < 0.001 and 0.015) than those without. The result was similar after adjustment with clinical variables and preoperative troponin T levels (hazard ratio = 1.30, 95% confidence interval [CI] = 1.03-1.65; P = 0.027). In sequential Cox analysis and net reclassification index, LVGLS had an incremental value for predicting the co-primary endpoints after non-cardiac surgery. Among the 538 (61.8%) participants who underwent serial troponin assay, LVGLS predicted MINS independently from the traditional risk factors (odds ratio = 3.54, 95% CI = 1.70-7.36; P = 0.001). Conclusions: Preoperative LVGLS has an independent and incremental prognostic value in predicting early postoperative cardiovascular events and MINS. Clinical Trial Registration: URL: https://trialsearch.who.int/. Unique identifiers: KCT0005147.ope

Artificial Intelligence-Enabled ECG Algorithm for the Prediction of Coronary Artery Calcification

Coronary artery calcium (CAC), which can be measured in various types of computed tomography (CT) examinations, is a hallmark of coronary artery atherosclerosis. However, despite the clinical value of CAC scores in predicting cardiovascular events, routine measurement of CAC scores is limited due to high cost, radiation exposure, and lack of widespread availability. It would be of great clinical significance if CAC could be predicted by electrocardiograms (ECGs), which are cost-effective and routinely performed during various medical checkups. We aimed to develop binary classification artificial intelligence (AI) models that predict CAC using only ECGs as input. Moreover, we aimed to address the generalizability of our model in different environments by externally validating our model on a dataset from a different institution. Among adult patients, standard 12-lead ECGs were extracted if measured within 60 days before or after the CAC scores, and labeled with the corresponding CAC scores. We constructed deep convolutional neural network models based on residual networks using only the raw waveforms of the ECGs as input, predicting CAC at different levels, namely CAC score ≥100, ≥400 and ≥1,000. Our AI models performed well in predicting CAC in the training and internal validation dataset [area under the receiver operating characteristics curve (AUROC) 0.753 ± 0.009, 0.802 ± 0.027, and 0.835 ± 0.024 for the CAC score ≥100, ≥400, and ≥1,000 model, respectively]. Our models also performed well in the external validation dataset (AUROC 0.718, 0.777 and 0.803 for the CAC score ≥100, ≥400, and ≥1,000 model, respectively), indicating that our model can generalize well to different but plausibly related populations. Model performance in terms of AUROC increased in the order of CAC score ≥100, ≥400, and ≥1,000 model, indicating that higher CAC scores might be associated with more prominent structural changes of the heart detected by the model. With our AI models, a substantial proportion of previously unrecognized CAC can be afforded with a risk stratification of CAC, enabling initiation of prophylactic therapy, and reducing the adverse consequences related to ischemic heart disease.ope

Cardiac Manifestations of Coronavirus Disease 2019 (COVID-19): a Multicenter Cohort Study

Background: This study aimed to investigate the cardiac manifestations of coronavirus disease 2019 (COVID-19). Methods: From February to March 2020, we prospectively and retrospectively enrolled consecutive patients diagnosed with COVID-19. Patient's data such as the demographic characteristics, symptoms, vital signs, laboratory and radiologic findings, electrocardiographic, and echocardiographic data, including the global longitudinal strain (GLS) of both ventricles, were obtained. Results: Forty patients (median age, 58 years; 50% men) were enrolled in the initial analysis. Patients were classified into severe and nonsevere groups based on the current guidelines. The 13 patients in the severe group were significantly older, had a greater prevalence of bilateral pneumonia and leukocytosis, and higher aspartate transaminase levels than patients in the nonsevere group. Patients in the severe group had a slightly lower left ventricular ejection fraction (LVEF) than those in the nonsevere group (median [interquartile range], 61.0% [58.5%, 62.3%] vs. 66.7% [60.6%, 69.8%], P = 0.015). In a subgroup of 34 patients in whom GLS could be analyzed, patients in the severe group had a significantly impaired left ventricular GLS (LVGLS) than those in the nonsevere group (-18.1% [-18.8%, -17.1%] vs. -21.7% [-22.9%, -19.9%], P = 0.001). There were no significant differences in total wall (RVGLStotal, -19.3% [-23.9%, -18.4%] vs. -24.3% [-26.0%, -22.6%], P = 0.060) and free wall (RVGLSfw, -22.7% [-27.2%, -18.6%] vs. -28.8% [-30.4%, -24.1%], P = 0.066) right ventricle GLS (RVGLS). Conclusion: Patients with severe COVID-19 had lower LVEF and LVGLS. RVGLS was not different between patients with severe and nonsevere COVID-19.ope

Red cell distribution width as a prognosticator in patients with heart failure

Aims: Increased red cell distribution width (RDW) is a poor prognostic factor in patients with heart failure (HF). However, only a few large-scale studies have identified the clinical utility of RDW after adjusting for covariates affecting RDW. Methods and results: From January 2010 to April 2021, we retrospectively enrolled patients diagnosed with HF from three referral hospitals with available RDW data (taken within 3 months of HF diagnosis) using an integrated clinical data system. Patients with an ejection fraction (EF) < 50% or HFA-PEFF (Heart Failure Association Pre-test assessment, Echocardiography and natriuretic peptide, Functional testing, Final aetiology) score ≥ 2 without severe valvular heart disease or coronary revascularization were enrolled. The primary endpoint was all-cause mortality, and cardiovascular mortality was also collected. Multivariable Cox regression analysis and stabilized inverse probability of treatment weighting (IPTW) were used to identify any association between RDW and all-cause death by balancing covariates or compounding factors. The global χ2 score was calculated and discrimination analysis was performed to evaluate the incremental value of RDW in predicting prognosis. Among the 6599 participants enrolled in this study, 1256 (19.0%) cases of all-cause death occurred, and the median duration of follow-up was 887 (interquartile range 351-1589) days. Elevated RDW at the initial diagnosis was associated with poor prognosis [cumulative incidence: 819 (30.2%) vs. 437 (11.2%), relative risk 1.58, 95% confidence interval (CI) 1.51-1.67, log-rank P < 0.001]. Multivariable Cox analysis showed that elevated RDW was a poor prognostic factor for the primary endpoint [hazard ratio (HR) 1.11, 95% CI 1.06-1.16, P < 0.001], independent of clinical risk factors, N-terminal pro-brain natriuretic peptide (NT-proBNP), and EF, which was concordant with the stabilized IPTW (HR 1.29, 95% CI 1.10-1.49, P < 0.001). Adding RDW to model composed of traditional risk factors, NT-proBNP, and echocardiographic parameters showed incremental prognostic value for predicting poor prognosis (area under the receiver operating characteristic curve, 0.799-0.826; P < 0.001). Conclusions: Increased RDW at the time of diagnosis is associated with poor prognosis in patients with HF, independent of clinical risk factors, such as NT-proBNP, and echocardiographic parameters. Therefore, RDW may aid in the management of these patients beyond traditional risk factors.ope

The validation of the dual antiplatelet therapy score in East Asians receiving percutaneous coronary intervention with exclusively second generation drug-eluting stents

Objectives: We investigated whether the dual antiplatelet therapy (DAPT) score (DS) predicts clinical outcome in an East-Asian population that received exclusively second generation drug-eluting stent (DES). Backgrounds: It is uncertain whether the DS could adequately risk stratify patients exclusively receiving second generation DES. Methods: From the Grand-DES registry, we evaluated patients who were treated with DAPT for at least 12 months and were event-free at 12 months after DES implantation. Patients were classified into two categories: high DS (≧2) (n = 3,157); and low DS (<2) (n = 5,226). The primary ischemic outcome was a composite of stent thrombosis and all myocardial infarction (MI), and the primary bleeding outcome was TIMI major or minor bleeding. A propensity score (PS)-matched analysis was done to correct for baseline differences between extended DAPT group and the conventional group. Results: Among 8,383 subjects, the primary ischemic outcome occurred in 48 patients (0.6%) and the primary bleeding outcome in 49 patients (0.6%). High DS was associated with a higher incidence of ischemic events (ischemic outcome: 0.8% vs. 0.4%, for high vs. low DS, Log-rank p = .039), but not with any differences in bleeding events (Log-rank p = .734). In the PS-matched analysis, extended group was associated with lower risk of composite endpoint of MI, stent thrombosis, or cardiac death in only the high DS group (1.8% vs. 3.7%, Log-rank p = .004; hazard ratio 0.45, 95% confidence interval 0.27-0.76; p = .003 after adjustment). Conclusions: The DS was an adequate risk stratifier for future ischemic events in East Asians receiving exclusively second generation DES. Trial registration: ClinicalTrials.gov NCT03507205.restrictio

Prognostic value of arterial stiffness in menopausal women

Objective: Because menopausal women have an increased cardiovascular risk, risk stratification is very crucial in this population. This study aimed to verify the prognostic value of arterial stiffness in menopausal women. Methods: We retrospectively analyzed 2,917 menopausal women (age >55y) without overt cardiovascular disease who underwent brachial-ankle pulse wave velocity measurement. The primary endpoint was a composite of clinical events, including all-cause death, nonfatal myocardial infarction, coronary revascularization, and stroke, hereafter referred to as major adverse cardiovascular events. Propensity score matching and inverse probability-treatment weighting analysis were used to balance differences in baseline participant characteristics. Results: The mean participant age was 66.8 ± 7.7 years. During a median follow-up period of 4.0 (interquartile range of 1.9-6.3) years, the primary outcome was noted in 56 cases (1.9%). Pulse wave velocity was significantly higher in participants with the primary outcome than in those without (1,947 ± 388 vs 1,690 ± 348 cm/s; P 1,613 cm/s was associated with increased risk of the primary endpoint in the same multivariable analysis (hazard ratio, 3.06; 95% confidence interval, 1.40-6.68; P = 0.005). The results were consistent after propensity score matching and inverse probability-treatment weighting analysis. Conclusions: Elevated brachial-ankle pulse wave velocity was associated with the occurrence of major adverse cardiovascular events in menopausal women without cardiovascular disease and may represent a useful screening tool.restrictio