Advancing Cardio-Oncology in Asia

Cardio-oncology is an emerging multi-disciplinary field, which aims to reduce morbidity and mortality of cancer patients by preventing and managing cancer treatment-related cardiovascular toxicities. With the exponential growth in cancer and cardiovascular diseases in Asia, there is an emerging need for cardio-oncology awareness among physicians and country-specific cardio-oncology initiatives. In this state-of-the-art review, we sought to describe the burden of cancer and cardiovascular disease in Asia, a region with rich cultural and socio-economic diversity. From describing the uniqueness and challenges (such as socio-economic disparity, ethnical and racial diversity, and limited training opportunities) in establishing cardio-oncology in Asia, and outlining ways to overcome any barriers, this article aims to help advance the field of cardio-oncology in Asia.

Elevated On-Treatment Diastolic Blood Pressure and Cardiovascular Outcomes in the Presence of Achieved Systolic Blood Pressure Targets

Background and Objectives@#This study aimed to investigate the association between cardiovascular events and 2 different levels of elevated on-treatment diastolic blood pressures (DBP) in the presence of achieved systolic blood pressure targets (SBP). @*Methods@#A nation-wide population-based cohort study comprised 237,592 patients with hypertension treated. The primary endpoint was a composite of cardiovascular death, myocardial infarction, and stroke. Elevated DBP was defined according to the Seventh Report of Joint National Committee (JNC7; SBP <140 mmHg, DBP ≥90 mmHg) or to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) definitions (SBP <130 mmHg, DBP ≥80 mmHg). @*Results@#During a median follow-up of 9 years, elevated on-treatment DBP by the JNC7 definition was associated with an increased risk of the occurrence of primary endpoint compared with achieved both SBP and DBP (adjusted hazard ratio [aHR], 1.14; 95% confidence interval [CI], 1.05–1.24) but not in those by the 2017 ACC/AHA definition. Elevated ontreatment DBP by the JNC7 definition was associated with a higher risk of cardiovascular mortality (aHR, 1.42; 95% CI, 1.18–1.70) and stroke (aHR, 1.19; 95% CI, 1.08–1.30). Elevated on-treatment DBP by the 2017 ACC/AHA definition was only associated with stroke (aHR, 1.10;95% CI, 1.04–1.16). Similar results were seen in the propensity-score-matched cohort. @*Conclusion@#Elevated on-treatment DBP by the JNC7 definition was associated a high risk of major cardiovascular events, while elevated DBP by the 2017 ACC/AHA definition was only associated with a higher risk of stroke. The result of study can provide evidence of DBP targets in subjects who achieved SBP targets.

Suboptimal Management Status of Younger Hypertensive Population in Korea

Background and Objectives@#Hypertension (HTN) is the most contributable risk factor for cardiovascular disease. May Measurement Month (MMM) is a global initiative to raise awareness of HTN and act as a temporary solution to the lack of screening programs worldwide. @*Methods@#An opportunistic cross-sectional survey of participants aged ≥18 was carried out in May 2019. Over 10,000 participants were recruited in the MMM 2019 Korea, with a slogan of “A simple measure to save lives – #checkyourpressure.” @*Results@#A total of 9,950 participants with valid clinical blood pressure (BP) data were used for analysis. All participants were Korean in ethnicity. The mean age was 57.2±21.2 years, 57.8% were females, and the mean body mass index was 23.4±3.3 kg/m 2 . Among the enrolled population, 20.1% were less than 30 years old, and 5.0% were 30–39 years old. 37.0% of the participants reported a previous diagnosis of HTN, and 91.3% of those diagnosed were on antihypertensive medications. Notably, more than 20% of the participants had not measured their BP during the last 12 months, and the awareness rate in the young hypertensive participants (aged <40) was less than 10%. Among hypertensive participants, the treatment rate was 69.3%, and the control rate among those taking medications was 61.2%. @*Conclusion@#MMM 2019 Korea campaign reported high BP control rates in individuals withHTN, reaching 60%. However, the awareness rate in young hypertensive participants was less than 10% along with suboptimal management status. The MMM 2019 Korea again raised the importance of regular BP measurement in the younger population.

Suboptimal Management Status of Younger Hypertensive Population in Korea

Background and Objectives@#Hypertension (HTN) is the most contributable risk factor for cardiovascular disease. May Measurement Month (MMM) is a global initiative to raise awareness of HTN and act as a temporary solution to the lack of screening programs worldwide. @*Methods@#An opportunistic cross-sectional survey of participants aged ≥18 was carried out in May 2019. Over 10,000 participants were recruited in the MMM 2019 Korea, with a slogan of “A simple measure to save lives – #checkyourpressure.” @*Results@#A total of 9,950 participants with valid clinical blood pressure (BP) data were used for analysis. All participants were Korean in ethnicity. The mean age was 57.2±21.2 years, 57.8% were females, and the mean body mass index was 23.4±3.3 kg/m 2 . Among the enrolled population, 20.1% were less than 30 years old, and 5.0% were 30–39 years old. 37.0% of the participants reported a previous diagnosis of HTN, and 91.3% of those diagnosed were on antihypertensive medications. Notably, more than 20% of the participants had not measured their BP during the last 12 months, and the awareness rate in the young hypertensive participants (aged <40) was less than 10%. Among hypertensive participants, the treatment rate was 69.3%, and the control rate among those taking medications was 61.2%. @*Conclusion@#MMM 2019 Korea campaign reported high BP control rates in individuals withHTN, reaching 60%. However, the awareness rate in young hypertensive participants was less than 10% along with suboptimal management status. The MMM 2019 Korea again raised the importance of regular BP measurement in the younger population.

Moving Beyond the Endothelium is Still Challenging-Complex Interplay between Endothelin and Reactive Oxygen Species in Pulmonary Arterial Hypertension

No abstract available.

The Safety and Utility of Dobutamine Stress Echocardiography for Pre-operative Risk Stratification in Orthotopic Liver Transplantation

No abstract available.

Current Awareness and Use of the Strain Echocardiography in Routine Clinical Practices: Result of a Nationwide Survey in Korea

BACKGROUND: Because conventional echocardiographic parameters have several limitations, strain echocardiography has often been introduced in clinical practice. However, there are also obstacles in using it in clinical practice. Therefore, we wanted to find the current status of awareness on using strain echocardiography in Korea. METHODS: We conducted a nationwide survey to evaluate current use and awareness of strain echocardiography from the members of the Korean Society of Echocardiography. RESULTS: We gathered total 321 questionnaires from 25 cardiology centers in Korea. All participants were able to perform or interpret echocardiographic examinations. All participating institutions performed strain echocardiography. Most of our study participants (97%) were aware of speckle tracking echocardiography and 185 (58%) performed it for clinical and research purposes. Two-dimensional strain echocardiography was the most commonly used modality and left ventricle (LV) was the most commonly used cardiac chamber (99%) for clinical purposes. Most of the participants (89%) did not think LV strain can replace LV ejection fraction (LVEF) in their clinical practice. The common reasons for not performing routine use of strain echocardiography was diversity of strain measurements and lack of normal reference value. Many participants had a favorable view of the future of strain echocardiography. CONCLUSION: Most of our study participants were aware of strain echocardiography, and all institutions performed strain echocardiography for clinical and research purposes. However, they did not think the LV strain values could replace LVEF. The diversity of strain measurements and lack of normal reference values were common reasons for not using strain echocardiography in clinical practice.

Impact of Contrast Echocardiography on Assessment of Ventricular Function and Clinical Diagnosis in Routine Clinical Echocardiography: Korean Multicenter Study

BACKGROUND: Fundamental echocardiography has some drawbacks in patients with difficult-to-image echocardiograms. The aim of this study is to evaluate impact of contrast echocardiography (CE) on ventricular function assessment and clinical diagnosis in routine clinical echocardiography. METHODS: Two hundred sixty patients were prospectively enrolled over 3 years in 12 medical centers in Korea. General image quality, the number of distinguishable segments, ability to assess regional wall motion, left ventricular (LV) apex and right ventricle (RV) visualization, LV ejection fraction, changes in diagnostic or treatment plan were documented after echocardiography with and without ultrasound contrast agent. RESULTS: Poor or uninterpretable general image was 31% before contrast use, and decreased to 2% (p<0.05) after contrast use. The average number of visualized LV segments was 9.53 before contrast use, and increased to 14.46 (p<0.001) after contrast use. The percentage of poor or not seen LV regional wall motion was decreased from 28.4% to 3.5% (p<0.001). The percentage of poor or not seen LV apex and RV was decreased from 49.4% to 2.4% (p<0.001), from 30.5% to 10.5% (p<0.001), respectively. Changes in diagnostic procedure and treatment plan after CE were 30% and 29.6%, respectively. CONCLUSION: Compared to fundamental echocardiography, CE impacted LV function assessment and clinical decision making in Korean patients who undergo routine echocardiography.

Normal Echocardiographic Measurements in a Korean Population Study: Part II. Doppler and Tissue Doppler Imaging

BACKGROUND: Hemodynamic and functional evaluation with Doppler and tissue Doppler study as a part of comprehensive echocardiography is essential but normal reference values have never been reported from Korean normal population especially according to age and sex. METHODS: Using Normal echOcaRdiographic Measurements in a KoreAn popuLation study subjects, we obtained normal reference values for Doppler and tissue Doppler echocardiography including tricuspid annular velocities according to current guidelines and compared values according to gender and age groups. RESULTS: Mitral early diastolic (E) and late diastolic (A) velocity as well as E/A ratio were significantly higher in women compared to those in men. Conversely, mitral peak systolic and late diastolic annular velocity in both septal and lateral mitral annulus were significantly lower in women compared to those in men. However, there were no significant differences in both septal and lateral mitral early diastolic annular (e') velocity between men and women. In both men and women, mitral E velocity and its deceleration time as well as both E/A and E/e' ratio considerably increased with age. There were no significant differences in tricuspid inflow velocities and tricuspid lateral annular velocities between men and women except e' velocity, which was significantly higher in women compared to that in men. However, changes in both tricuspid inflow and lateral annular velocities according to age were similar to those in mitral velocities. CONCLUSION: Since there were significant differences in Doppler and tissue Doppler echocardiographic variables between men and women and changes according to age were even more considerable in both gender groups, normal Doppler echocardiographic values should be differentially applied based on age and sex.

Normal 2-Dimensional Strain Values of the Left Ventricle: A Substudy of the Normal Echocardiographic Measurements in Korean Population Study

BACKGROUND: It is important to understand the distribution of 2-dimensional strain values in normal population. We performed a multicenter trial to measure normal echocardiographic values in the Korean population. METHODS: This was a substudy of the Normal echOcardiogRaphic Measurements in KoreAn popuLation (NORMAL) study. Echocardiographic specialists measured frequently used echocardiographic indices in healthy people according to a standardized method at 23 different university hospitals. The strain values were analyzed from digitally stored images. RESULTS: Of a total of 1003 healthy participants in NORMAL study, 2-dimensional strain values were measured in 501 subjects (265 females, mean age 47 ± 15 years old) with echocardiographic images only by GE echocardiographic machines. Interventricular septal thickness, left ventricular (LV) posterior wall thickness, systolic and diastolic LV dimensions, and LV ejection fraction were 7.5 ± 1.0 mm, 7.4 ± 1.0 mm, 29.9 ± 2.8 mm, 48.9 ± 3.6 mm, and 62 ± 4%, respectively. LV longitudinal systolic strain (LS) values of apical 4-chamber (A4C) view, apical 3-chamber (A3C) view, apical 2-chamber (A2C) view, and LV global LS (LVGLS) were −20.1 ± 2.3, −19.9 ± 2.7, −21.2 ± 2.6, and −20.4 ± 2.2%, respectively. LV longitudinal systolic strain rate (LVLSR) values of the A4C view, A3C view, A2C view, and LV global LSR (LVGLSR) were −1.18 ± 0.18, −1.20 ± 0.21, −1.25 ± 0.21, and −1.21 ± 0.21(−s), respectively. Females had lower LVGLS (−21.2 ± 2.2% vs. −19.5 ± 1.9%, p < 0.001) and LVGLSR (−1.25 ± 0.18(−s) vs. −1.17 ± 0.15(−s), p < 0.001) values than males. CONCLUSION: We measured LV longitudinal strain and strain rate values in the normal Korean population. Since considerable gender differences were observed, normal echocardiographic cutoff values should be differentially applied based on sex.

The Clinical Impact of Bedside Contrast Echocardiography in Intensive Care Settings: A Korean Multicenter Study

BACKGROUND AND OBJECTIVES: We assessed the ability of portable echocardiography (with contrasts) to clearly delineate the cardiac structure, and evaluated the impact of its use on the diagnosis and management of critically ill patients in Korea. SUBJECTS AND METHODS: We prospectively enrolled 123 patients (mean age 66+/-16 years), who underwent portable transthoracic echocardiography (with contrast) for image enhancement at 12 medical centers. The quality of the global left ventricular (LV) images, the number of the regional LV segments visualized, the ability to visualize the LV apex and the right ventricle (RV), and any changes in the diagnostic procedure and treatment strategy were compared before and after the contrast. RESULTS: Of the 123 patients, 52 (42%) were using mechanical ventilators. The amount of poor or uninterpretable images decreased from 48% to 5% (p<0.001), after the contrast. Before the contrast, 15.6+/-1.1 of 16 LV segments were seen, which improved to 15.9+/-0.6 segments (p=0.001) after the contrast. The ability to visualize the LV apex increased from 47% to 94% (p<0.001), while the inability to clearly visualize the RV decreased from 46% to 19% (p<0.001). Changes in the diagnostic procedure (for example, not requiring other types of imaging studies) were observed in 18% of the patients, and the treatment plan (medication) was altered in 26% of patients after the contrast echocardiography. CONCLUSION: The use of a contrast agent during the portable echocardiography, in intensive care settings, can improve the image quality and impact the diagnostic procedures and treatment for Korean patients.

Normal Echocardiographic Measurements in a Korean Population Study: Part I. Cardiac Chamber and Great Artery Evaluation

BACKGROUND: Measurement of the cardiac chamber is essential, and current guidelines recommend measuring and reporting values for both sides of the cardiac chamber during echocardiographic evaluation. Normal echocardiographic reference values have been suggested previously, but detailed information about right-sided chambers and values according to gender was not included. METHODS: This is a prospective multicenter (23 centers) study evaluating normal Korean adult subjects using comprehensive echocardiography. We included normal adult subjects (age; 20-79 years old) who had no significant cardiac disorders or illnesses, such as hypertension or diabetes, which could affect cardiac structure and function. We measured the cardiac chamber including both right and left ventricles as well as atria according to current echocardiography guidelines and compared values according to gender and age groups. RESULTS: A total of 1003 subjects were evaluated and the mean age was 48 +/- 16 years. Left ventricular (LV) dimensions increased, but LV volume decreased in older subjects. Right ventricular (RV) area decreased in women and older subjects, and the RV long-axis dimension showed a similar trend. Left atrial (LA) volume increased in men but there were no differences in LA volume index between men and women. The dimension of great arteries increased in men and older subjects. CONCLUSION: Since there were considerable differences between men and women and in the different age groups, and the trends differed significantly between different echo variables, normal echocardiographic cutoff values should be differentially applied based on age and gender.

The Value of Assessing Myocardial Deformation at Recovery after Dobutamine Stress Echocardiography

BACKGROUND: The purpose of this study was to evaluate whether performing an assessment of myocardial deformation using speckle tracking imaging during the recovery period after dobutamine stress echocardiography (DSE) allows detection of significant coronary artery disease (CAD) in patients with chest discomfort. METHODS: DSE and coronary angiography were performed in 44 patients with chest discomfort. The mean global longitudinal peak systolic strain (GLS) was measured at rest, at low stress (dobutamine infusion rate of 10 microg/kg/min) and at recovery (5 min after cessation of dobutamine infusion) of DSE using automated function imaging with apical views. Fractional flow reserve (FFR) was also performed in patients with intermediate coronary stenosis. CAD was defined as having a > or = 70% diameter stenosis on coronary angiography or as having a FFR < 0.8. Patients were divided two groups based on the absence or presence of CAD [CAD (-) group vs. CAD (+) group]. RESULTS: There were no significant differences in the clinical characteristics and results of conventional echocardiography between the two groups. GLS at recovery was lower in the CAD (+) group than in the CAD (-) group (-18.0 +/- 3.4% vs. -21.0 +/- 1.9%, p = 0.003). The optimal cutoff of GLS at recovery for detection of CAD was -19% (sensitivity of 70.6%, specificity of 83.3%). CONCLUSION: Assessment of GLS at recovery of DSE is a reliable and objective method for detection of CAD. This finding may suggest that systolic myocardial stunning remains even after recovery of wall motion abnormalities in patients with CAD.

APACHE II Score, Rather Than Cardiac Function, May Predict Poor Prognosis in Patients With Stress-Induced Cardiomyopathy

While the disease course of stress-induced cardiomyopathy (SIC) is usually benign, it can be fatal. The prognostic factors to predict poorer outcome are not well established, however. We analyzed the Acute Physiology And Chronic Health Evaluation (APACHE) II score to assess its value for predicting poor prognosis in patients with SIC. Thirty-seven consecutive patients with SIC were followed prospectively during their hospitalization. Clinical factors, including APACHE II score, coronary angiogram, echocardiography and cardiac enzymes at presentation were analyzed. Of the 37 patients, 27 patients (73%) were women. The mean age was 66.1 +/- 15.6 yr, and the most common presentation was chest pain (38%). Initial echocardiographic left ventricular ejection fraction (EF) was 42.5% +/- 9.3%, and the wall motion score index (WMSI) was 1.9 +/- 0.3. Six patients (16%) expired during the follow-up period of hospitalization. Based on the analysis of characteristics and clinical factors, the only predictable variable in prognosis was APACHE II score. The patients with APACHE II score greater than 20 had tendency to expire than the others (P = 0.001). Based on present study, APACHE II score more than 20, rather than cardiac function, is associated with mortality in patients with SIC.

Pharmacokinetic and Pharmacodynamic Study Determines Factors Affecting Blood Pressure Response to Valsartan

BACKGROUND: Valsartan is an angiotensin II receptor blocker and is used for patient with hypertension. Although response to valsartan varies each individual, there is no study about factors affecting the variability of valsartan response. METHODS: To investigate the effects of valsartan on the baseline characteristics of blood pressure, single group, open label, pre- and post-comparison clinical study was conducted. Total 21 male Korean volunteers were enrolled. Each subject was administered no drugs in first period and valsartan 80 mg (Diovan HCT) in second period. For pharmacodynamic analysis, 24 hours blood pressure changes were monitored by ambulatory blood pressure monitoring. Twenty-four hour blood pressure changes were matched to valsartan concentration and analyzed by correlation analysis. Changes in blood pressure pattern were also analyzed. Subjects were divided into responder, non-responder, and reverse responder according to pre- and post- 24 hours blood monitoring results. For determination of pharmacokinetic parameters, plasma concentration of valsartan was measured by a validated ultra-performance liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters including area under the plasma concentration versus time curve from 0 hour to the last measurable concentration (AUCt), area under the plasma concentration versus time curve extrapolated to infinity, maximum plasma concentration (Cmax), and time required to reach maximum plasma concentration (Tmax) were calculated by noncompartmental models in the BA-CALC 2008 program ver. 1.0.0. RESULTS: There were no significant associations between blood pressure changes and pharmacokinetic parameters of valsartan. Blood pressure pattern change analysis showed significant results. For AUCt, total amount of absorbed valsartan was 25,808 +/- 6,863.0 ng.hr/mL, 20,683 +/- 8,782.7 ng.hr/mL, and 12,502 +/- 5,566.6 ng.hr/mL in responder, non-responder, and reverse responder, respectively (p = 0.041). In C max, maximum concentration of valsartan was 4,314 +/- 1,522.6 ng/mL, 2,588 +/- 1,273.9 ng/mL, and 2,056 +/- 1,075.5 ng/mL, respectively. CONCLUSIONS: These results showed that response to valsartan was not associated with blood concentration in healthy volunteers and changes in blood pressure patterns to valsartan might be associated with the amount of drugs which are absorbed to subjects.

Early Cardiac Valvular Changes in Ankylosing Spondylitis: A Transesophageal Echocardiography Study

BACKGROUND: This study was conducted to determine the early cardiac valvular changes in young male ankylosing spondylitis (AS) patients. METHODS: A total of 70 AS patients on treatment without clinical cardiac symptoms were divided into group I ( or = 10 years, n = 20) depending on their disease duration after first diagnosis. Twenty-five healthy volunteers were selected as control subjects. All the subjects underwent transthoracic and transesophageal echocardiography, electrocardiography, and rheumatologic evaluation for AS patients. RESULTS: The thickness of both the aortic and mitral valve was more increased in AS patients than in controls. Aortic valve thickness over 1.3 mm could predict AS with a sensitivity of 73% and specificity of 76%. The prevalence of aortic valve thickening was higher in the AS group compared to the controls. The prevalence of aortic and mitral regurgitation was very low and there was no difference between the controls and the patients. The aortic valve thickening was related to longer disease duration, high blood pressure, disease activity and inflammatory markers. CONCLUSION: Thickening of the aortic and mitral valve was observed without regurgitation in male AS patients early in the course of their disease without clinical cardiac manifestations. This subclinical change of aorto-mitral valve in early AS should be considered and followed up to determine its prognostic implication and evolution.

Early Cardiac Valvular Changes in Ankylosing Spondylitis: A Transesophageal Echocardiography Study

BACKGROUND: This study was conducted to determine the early cardiac valvular changes in young male ankylosing spondylitis (AS) patients. METHODS: A total of 70 AS patients on treatment without clinical cardiac symptoms were divided into group I ( or = 10 years, n = 20) depending on their disease duration after first diagnosis. Twenty-five healthy volunteers were selected as control subjects. All the subjects underwent transthoracic and transesophageal echocardiography, electrocardiography, and rheumatologic evaluation for AS patients. RESULTS: The thickness of both the aortic and mitral valve was more increased in AS patients than in controls. Aortic valve thickness over 1.3 mm could predict AS with a sensitivity of 73% and specificity of 76%. The prevalence of aortic valve thickening was higher in the AS group compared to the controls. The prevalence of aortic and mitral regurgitation was very low and there was no difference between the controls and the patients. The aortic valve thickening was related to longer disease duration, high blood pressure, disease activity and inflammatory markers. CONCLUSION: Thickening of the aortic and mitral valve was observed without regurgitation in male AS patients early in the course of their disease without clinical cardiac manifestations. This subclinical change of aorto-mitral valve in early AS should be considered and followed up to determine its prognostic implication and evolution.

Cardiac Sarcoidosis: Oldies but Not Goodies

No abstract available.

Treadmill Exercise Stress Echocardiography in Patients With No History of Coronary Artery Disease: A Single-Center Experience in Korean Population

BACKGROUND AND OBJECTIVES: Treadmill exercise stress echocardiography (TSE) has superior diagnostic accuracy than exercise electrocardiography (ECG). The objectives of the study are 1) to define the diagnostic accuracy and safety of TSE in patients without a history of coronary artery disease (CAD), 2) to identify the clinical characteristics that predict positive TSE results and 3) to assess the differential predictive value between TSE and concomitant exercise ECG in a Korean population. SUBJECTS AND METHODS: A total of 1,287 patients among 1,500 consecutive patients with no prior history of CAD and who were referred for TSE during a 4-year 3-month period were enrolled. RESULTS: Of the 1,287 patients, 95 (7.4%) showed positive TSE results (newly developed regional wall motion abnormality). Among the 154 patients with coronary angiography, 94 patients (61%) showed significant CAD (30 of 77 patients with negative TSE results and 64 of 77 patients with positive TSE results). The TSE positive population had more cardiovascular risk factors and showed a higher Duke treadmill score and wall motion score index than the TSE negative group. TSE showed relatively good sensitivity (68%), specificity (78%) and positive and negative predictive values (83% and 61%, respectively), and TSE also had higher diagnostic accuracy than concomitant exercise ECG (72% vs. 64%, respectively). CONCLUSION: TSE is safe and offers greater diagnostic power for CAD than exercise ECG in Korean population without a history of CAD. Its prognostic value in this population needs to be confirmed in a larger prospective study.

Heavy Coronary Calcium Mimicking In-Stent Restenosis

No abstract available.