Current knowledge for the risk factors of early permanent pacemaker implantation following transcatheter aortic valve replacement and what is next for the primary prevention?

In this editorial, we comprehensively summarized the preoperative risk factors of early permanent pacemaker implantation after transcatheter aortic valve replacement (TAVR) among patients with severe aortic stenosis from several renowned clinical studies and focused on the primary prevention of managing the modifiable factors, e.g., paroxysmal atrial fibrillation before the TAVR.

Electrocardiographic and echocardiographic predictors of greater carotid intima-media thickness in tactical athletes: The CHIEF atherosclerosis study.

OBJECTIVE: Both electrocardiographic and echocardiographic left ventricular hypertrophy (LVH) have been reported with an association with greater carotid intima-media thickness (cIMT), a marker of subclinical atherosclerosis in patients with hypertension, while the associations are unclear in physically fit young adults. METHODS: A total of 1822 Taiwanese military personnel, aged 18-40 years, received an annual health examination including electrocardiography (ECG) and echocardiography in 2018-2020. Left carotid bulb cIMT was measured by high-resolution ultrasonography. Multiple logistic regression analysis with adjustments for age, sex, smoking, alcohol consumption, body mass index, mean blood pressure, and physical fitness was used to determine the associations between echocardiographic and ECG parameters and the highest quintile of cIMT (≥0.8 mm). RESULTS: Cornell-based LVH, Myers et al.-based RVH and heart rate ≥75/min were associated with cIMT ≥0.8 mm [odds ratios (ORs) and 95% confidence intervals: 1.54 (1.01, 2.35), 1.66 (1.18, 2.33), and 1.39 (1.06, 1.83), respectively], while echocardiographic LVH defined as ≥46.0 g/m2.7 for men and ≥38.0 g/m2.7 for women was inversely associated with cIMT ≥0.8 mm [OR: 0.45 (0.24, 0.86)]. CONCLUSION: In tactical athletes of military, the associations of ECG and echocardiographic LVH with cIMT were in opposite directions. Higher physical fitness may cause cardiac muscle hypertrophy and reduce the atherosclerosis severity, possibly leading to the paradoxical echocardiographic finding. This study suggests that ECG-based LVH remains a good marker of subclinical atherosclerosis in our military population.

Association Between Dental Calculus and Hypertension Phenotypes in Highly Fit Adults: CHIEF Oral Health Study.

BACKGROUND: Poor oral health evaluated by presence of dental calculus has been associated with hypertension (HTN) among middle- and old-aged adults. However, it is unclear for the association of HTN phenotypes with dental calculus in young adults. METHODS: This study examined the association between dental calculus and HTN in 5,345 military personnel, aged 19-45 years, without antihypertensive medications therapy in Taiwan from 2018 to 2021. Dental calculus was defined as presence of supragingival calculus in any teeth, except impacted teeth, and third molar. Combined HTN (CHTN) was diagnosed as systolic blood pressure (SBP) ≥130 mm Hg and diastolic blood pressure (DBP) ≥80 mm Hg. Isolated systolic and diastolic HTN were, respectively, defined as SBP ≥130 mm Hg only (ISHTN) and DBP ≥80 mm Hg only (IDHTN). Multiple logistic regression with adjustments for sex, age, toxic substance use, anthropometrics, lipid profiles, fasting glucose, and blood leukocyte counts were used to determine the association between dental calculus and HTN phenotypes in young adults. RESULTS: The prevalence of those with dental calculus, CHTN, ISHTN, and IDHTN was 20.8%, 10.8%, 10.2%, and 7.0%, respectively. The dental calculus was associated a greater possibility with CHTN [odds ratio (OR) and 95% confidence interval: 1.60 (1.31-1.95)]. However, the associations of dental calculus with ISHTN and IDHTN were null [OR: 1.05 (0.81-1.27) and 1.12 (0.86-1.46), respectively]. CONCLUSIONS: Our findings suggest that among young adults, poor oral health manifested by presence of dental calculus was associated with a greater possibility of CHTN, while not for ISHTN and IDHTN.

12-lead ECG signal processing and atrial fibrillation prediction in clinical practice.

BACKGROUND: Because clinically used 12-lead electrocardiography (ECG) devices have high falsepositive errors in automatic interpretations of atrial fibrillation (AF), they require substantial improvements before use. OBJECTIVE: A clinical 12-lead ECG pre-processing method with a parallel convolutional neural network (CNN) model for 12-lead ECG automatic AF recognition is introduced. METHODS: Raw AF diagnosis data from a 12-lead ECG device were collected and analyzed by two cardiologists to differentiate between true- and false-positives. Using a stationary wavelet transform (SWT) and independent component analysis (ICA) noise reduction was conducted and baseline wandering was corrected for the raw signals. AF patterns were learned and predicted using a parallel CNN deep learning (DL) model. (1) The proposed method alleviates the decreased ECG QRS amplitude enhances the signal-to-noise ratio and clearly shows atrial and ventricular activities. (2) After training, the CNNbased AF detector significantly reduced false-positive errors. The precision of AF diagnosis increased from 77.3% to 94.0 ± 1.5% as compared to ECG device interpretation. For AF screening, the model showed an average sensitivity of 96.8 ± 2.2%, specificity of 79.0 ± 5.8%, precision of 94.0 ± 1.5%, F1-measure of 95.2 ± 1.0%, and overall accuracy of 92.7 ± 1.5%. CONCLUSIONS: The method can bridge the gap between the research and clinical practice The ECG signal pre-processing and DL-based AF interpretation can be rapidly implemented clinically.

Obesity Phenotypes and Electrocardiographic Characteristics in Physically Active Males: CHIEF Study.

Background: Metabolically unhealthy obesity (MUO) has been associated with surface electrocardiographic (ECG) left ventricular hypertrophy (LVH), left atrial enlargement (LAE), and inferior T wave inversions (TWI) in the middle- and old-aged populations. However, the relationship between obesity phenotypes and these ECG abnormalities in physically active young adults is yet to be determined. Methods: A total of 2,156 physically active military males aged 18-50 in Taiwan were analyzed. Obesity and metabolically unhealthy status were, respectively, defined as the body mass index ≥27 kg/m2 and the presence of metabolic syndrome based on the ATPIII criteria for Asian male adults. Four groups were classified as the metabolically healthy non-obesity (MHNO, n = 1,484), metabolically unhealthy non-obesity (MUNO, n = 86), metabolically healthy obesity (MHO, n = 376), and MUO (n = 210). ECG-LVH was based on the Sokolow-Lyon and Cornell voltage criteria, ECG-LAE was defined as a notched P wave ≥0.12 s in lead II or a notch of ≥0.04 s, and inferior TWI was defined as one negative T wave axis in limb leads II, III, or aVF. Physical performance was evaluated by time for a 3-km run. Multiple logistic regression analysis with adjustment for age, smoking, alcohol drinking, and physical performance was utilized to investigate the associations between obesity phenotypes and the ECG abnormalities. Results: As compared to MHNO, MUNO, MHO, and MUO were associated with lower risk of Sokolow-Lyon-based ECG-LVH [odds ratios (OR) and 95% confidence intervals: 0.80 (0.51-1.25), 0.46 (0.36-0.58), and 0.39 (0.28-0.53), respectively; p for trend <0.001], and with greater risk of ECG-LAE [OR: 0.87 (0.44-1.72), 2.34 (1.77-3.10), and 3.02 (2.13-4.28), respectively; p for trend <0.001] and inferior TWI [OR: 2.21 (0.74-6.58), 3.49 (1.97-6.19), and 4.52 (2.38-8.60), respectively; p for trend <0.001]. However, no associations between obesity phenotypes and Cornell-based ECG-LVH were found. Conclusion: In physically active young males, obesity was associated with higher risk of ECG-LAE and inferior TWI, whereas the risk between obesity and ECG-LVH might vary by the ECG criteria, possibly due to a high prevalence of exercise induced-LVH in military and greater chest wall thickness in obesity. The cardiovascular prognosis of ECG-LVH in physically active obese adults requires further study.

Athlete's Heart Assessed by Sit-Up Strength Exercises in Military Men and Women: The CHIEF Heart Study.

BACKGROUND: Greater changes in cardiac structure and function in response to physical training have been observed more often in male athletes than in female athletes compared with their sedentary controls. However, studies for the sex-specific cardiac remodeling related to strength exercises in Asian athletes are rare. METHODS: This study included 580 men and 79 women, with an average age of 25 years, for a 6-month military training program in Taiwan. Both men and women attended a 2-min sit-up test to assess muscular strength after the training. The test performance falling one standard deviation above the mean (16%) was to define the superior eliteness of athletes. Cardiac structure and function were investigated by electrocardiography and echocardiography for men and women. Multiple logistic regression was used to determine the predictors of elite athlete status. RESULTS: In men, greater QTc interval, left ventricular mass adjusted to body surface area (LVMI), lateral mitral E'/A' ratio and right ventricular systolic pressure, and lower diastolic blood pressure were independent predictors of elite strength athletes in the sit-up test [odds ratio (OR) and 95% confidence intervals: 1.01 (1.00, 1.02), 1.02 (1.00, 1.04), 1.45 (1.06, 1.98), 1.13 (1.06, 1.23), and 0.96 (0.93, 0.99), respectively. In contrast, in women, the greater right ventricular outflow tract dimension was the only independent predictor of elite strength athletes in the sit-up test [OR: 1.26 (1.04, 1.53)]. CONCLUSIONS: In the 2-min sit-up test, cardiac characteristics differ between elite male and female athletes. While greater QTc interval, LVMI, and diastolic function of left ventricle predict the eliteness of male strength athletes, greater right ventricular chamber size characterizes elite female strength athletes.

Tobacco Smoking and Association between Betel Nut Chewing and Metabolic Abnormalities Among Military Males: The CHIEF Study.

AIM: To investigate the effect of smoking and alcohol intake on the association between betel nut chewing and each metabolic abnormality. BACKGROUND: Betel nut chewing has been associated with metabolic syndrome. OBJECTIVE: Whether the association is affected by tobacco or alcohol use is not clarified so far. METHODS: The authors conducted a cross-sectional study using 6,657 military males, aged 18-50 years in eastern Taiwan in 2013-2014. Metabolic syndrome was defined according to the International Diabetes Federation's ethnic criteria for Asians. The population was classified as non-betel nut chewers (N =5,749), current chewers with both tobacco and alcohol use (N =615), and current chewers without tobacco and/or alcohol use (N =293). Multiple logistic regression analyses were stepwise adjusted for the confounders including alcohol and tobacco use to determine the association of betel chewing with the metabolic abnormalities. RESULTS: As compared to the non-current chewers, the current chewers with both tobacco/alcohol use and those without had a higher risk of metabolic syndrome (odds ratios (OR) and 95% confidence intervals: 2.46 (2.00-3.02), and 2.04 (1.53-2.73), respectively) after controlling for age, service specialty, total cholesterol levels ≥200 mg/dL and exercise frequency (model 1). The association did not change much in the two chewing groups after additionally adjusting for alcohol consumption (model 2) (OR: 2.49 (1.99-3.12), and 2.04 (1.52-2.73), respectively), whereas the relationship reduced significantly in the chewers with both tobacco/alcohol use rather than those without after further adjusting for smoking (model 3) (OR: 2.18 (1.71-2.78) and 2.02 (1.51-2.71), respectively). This was in parallel with the pattern for the association of betel nut chewing with serum triglycerides >150 mg/dL in the chewers with both tobacco/alcohol use and those without in model 1 (OR: 2.90 (2.40-3.51) and 1.90 (1.45-2.49), respectively, p =0.011), in model 2 (OR: 2.82 (2.30-3.46) and 1.89 (1.44-2.49), respectively, p =0.040), and in model 3 (2.26 (1.81-2.81) and 1.87 (1.42-2.45), respectively, p =0.76). CONCLUSION: Our findings suggest that tobacco smoking but not alcohol intake could increase the relationship of betel nut chewing with metabolic syndrome, which is likely mediated by a synergic effect on increasing serum triglycerides levels.

Association of red blood cell size and physical fitness in a military male cohort: The CHIEF study.

Anemia manifested as reduced red blood cell (RBC) amounts or hemoglobin levels has been associated with lower cardiorespiratory fitness. However, the relationship of smaller RBC with physical fitness was unknown. We included 2933 non-anemic military males (hemoglobin levels: 11.1-15.9 g/dL and mean corpuscular volume (MCV) <100 fL) in Taiwan during 2014. Aerobic fitness was assessed by time for a 3000-meter run, and anaerobic fitness was evaluated by numbers of sit-ups and push-ups, each performed within 2 minutes. Multiple linear and logistic regression models adjusting for age, service specialty, lipid profiles, and hemoglobin levels were used to determine the associations. Microcytosis and normocytosis were defined as MCV ≤ 70 fL (n = 190) and MCV > 70 fL (n = 2743), respectively. The linear regression shows that as compared with microcytosis, normocytosis was associated with more numbers of sit-ups performed within 2 minutes (ß = 1.51, P-value = 0.02). The logistic regression also reveals that those males with microcytosis had higher probability as the worst 10% performers in the 2-minute push-up test (odds ratio: 1.91, 95% confidence intervals: 1.18-3.12). By contrast, there was no association of microcytosis with 3000-meter running time. Our study suggests that non-anemic microcytosis was associated with lower anaerobic fitness but not with aerobic fitness. Whether the causative factors for microcytosis such as iron deficiency status and thalassemia trait unavailable in the study might account for the relationship needs further investigations.

Association of Single Measurement of dipstick proteinuria with physical performance of military males: the CHIEF study.

BACKGROUND: Proteinuria, a marker of kidney injury, may be related to skeletal muscle loss. Whether the severity of proteinuria is associated with physical performance is unclear. METHODS: We examined the association of proteinuria severity with physical performance cross-sectionally in 3357 military young males, free of chronic kidney disease, from the cardiorespiratory fitness and hospitalization events in armed Forces (CHIEF) study in Taiwan. The grades of proteinuria were classified according to one dipstick urinalysis which were collected at morning after an 8-h fast as unremarkable (0, +/-, and 1+), moderate (2+) and severe (3+ and 4+). Aerobic physical performance was evaluated by time for a 3000-m run and anaerobic physical performance was evaluated by numbers of 2-min sit-ups and 2-min push-ups, separately. Multiple linear regressions were used to determine the relationship. RESULTS: As compared with unremarkable proteinuria, moderate and severe proteinuria were dose-dependently correlated with 3000-m running time (ß: 4.74 (95% confidence intervals (CI): - 0.55, 10.02) and 7.63 (95% CI: 3.21, 12.05), respectively), and inversely with numbers of 2-min push-ups (ß = - 1.13 (- 1.97, - 0.29), and - 1.00 (- 1.71, - 0.28), respectively) with adjustments for age, service specialty, body mass index, blood pressure, alcohol intake, smoking, fasting plasma glucose, blood urea nitrogen, serum creatinine and physical activity. However, there was no association between proteinuria severity and 2-min sit-ups. CONCLUSIONS: Our findings show a relationship of dipstick proteinuria with aerobic physical performance and parts of anaerobic physical performance in military healthy males. This mechanism is not fully understood and requires further investigations.

Psychological stress and long-term blood pressure variability of military young males: The cardiorespiratory fitness and hospitalization events in armed forces study.

BACKGROUND: Acute stress might increase short-term heart rate variability and blood pressure variability (BPV); however, chronic stress would not alter short-term BPV in animal models. AIM: To examine the association of psychological stress with long-term BPV in young male humans. METHODS: We prospectively examined the association of chronic psychological stress with long-term BPV in 1112 healthy military males, averaged 32.2 years from the cardiorespiratory fitness and hospitalization events in armed forces study in Taiwan. Psychological stress was quantitatively evaluated with the Brief Symptom Rating Scale (BSRS-5), from the least symptom of 0 to the most severe of 20, and the five components of anxiety, insomnia, depression, interpersonal sensitivity, and hostility (the severity score in each component from 0 to 4). Long-term BPV was assessed by standard deviation (SD) for systolic and diastolic blood pressure (SBP and DBP), and average real variability (ARV), defined as the average absolute difference between successive measurements of SBP or DBP, across four visits in the study period from 2012 to 2018 (2012-14, 2014-15, 2015-16, and 2016-18). RESULTS: The results of multivariable linear regressions showed that there were no correlations of the BSRS-5 score with SDSBP, SDDBP, ARVSBP, and ARVDBP after adjusting for all the covariates [ß(SE): -0.022 (0.024), -0.023 (0.026), -0.001 (0.018), and 0.001 (0.020), respectively; P > 0.05 for all]. In addition, there were also no correlations between each component of the BSRS score and the long-term BPV indexes. CONCLUSION: Our findings suggest that chronic psychological stress might not be associated with long-term BPV in military young male humans.

Physical Fitness and Long-term Blood Pressure Variability in Young Male Military Personnel.

AIMS: The aim of this study is to investigate the association of physical fitness with longterm Blood Pressure Variability (BPV) in young male adults. METHODS: 1,112 healthy military males, aged 18-40 years (mean age, 32 years), in Taiwan were included for the current analysis. Resting blood pressures were measured over the right upper arm in a sitting position every two years from 2012 to 2018 (2012-14, 2014-15, 2015-16, 2016-18). Long-term BPV by Standard Deviation (SDSBP and SDDBP) and Average Real Variability (ARVSBP and ARVDBP) were assessed across 4 visits during the study period. Aerobic fitness was evaluated by the time taken for a 3000-meter run test, and anaerobic fitness was evaluated by the number of 2-minute sit-ups and 2-minute push-ups. RESULTS: After adjusting the systolic and diastolic blood pressure, the time for a 3000-meter run was associated with ARVSBP, SDSBP, and SDDBP (ß [SE]: 0.007 [0.002], 0.004 [0.002], and 0.005 [0.002], respectively, all p <0.05) but not with ARVDBP. In addition, the number of 2-minute sit-ups was inversely associated with ARVSBP (ß [SE]: -0.041 [0.017], p =0.01) but not with ARVDBP, SDSBP, and SDDBP. There was no association of the number of 2-minute push-ups with the BPV indexes. After additionally adjusting the age, body mass index, and other covariates, all the associations were found to be not significant. CONCLUSION: It was found that there was no association of physical fitness with long-term BPV in young male military personnel. Previous studies have shown no association with cardiorespiratory fitness in the elderly. This study further increased the knowledge of a null association between anaerobic fitness and long-term BPV.

Association between mild anemia and physical fitness in a military male cohort: The CHIEF study.

Anemia defined as reduced hemoglobin levels of red blood cells may carry less oxygen to skeletal muscle and impair physical performance. Previous studies have shown that exercise intolerance was related to moderate or severe anemia, however, the relationship to mild anemia was unknown. We investigated the cross-sectional association of mild anemia defined as a hemoglobin level of 10.0-13.9 g/dL with physical fitness in 3,666 military young males in Taiwan in 2014. Aerobic fitness was evaluated by 3000-meter run test, and anaerobic fitness was evaluated by 2-minute sit-ups and 2-minute push-ups, respectively. Multiple logistic regressions for the best 10% and the worst 10% performers were used to determine the relationship. There were 343 mild anemic males in whom 47.8% were microcytic anemia and 3,323 non-anemic males for the analysis. The multiple logistic regression shows that as compared with non-anemic males, mild anemic males were more likely to be the worst 10% performers in the 3000-meter run test (odds ratios (OR) and 95% confidence intervals: 1.47, 1.01-2.14) after adjusting for age, service specialty, body mass index, waist size, mean blood pressure, unhealthy behaviors, lipid profiles, and exercise frequency. On the contrary, mild anemic males had higher possibility to be the best 10% performers in the 2-minute push-ups test (OR: 1.48, 1.08-2.04). However, there was no association between mild anemia and 2-minute sit-ups. Our findings suggest that unspecified mild anemia might be associated with lower cardiorespiratory fitness but not with anaerobic fitness in physically active military males.

Sex-Specific Association Between Serum Uric Acid and Elevated Alanine Aminotransferase in a Military Cohort: The CHIEF Study.

AIM: The study was conducted in order to examine the sex-specific association of serum uric acid (SUA) levels with elevated serum alanine aminotransferase (ALT) in a Taiwanese military cohort. METHODS: We made a cross-sectional examination of the sex-specific relationship using 6728 men and 766 women, aged 18-50 years from a large military cohort in Taiwan. SUA levels within the reference range (<7.0 mg/dL for men and <5.7 mg/dL for women respectively) were divided into quartiles and SUA levels greater than the upper reference limits were defined as hyperuricemia. Elevated ALT levels were defined as ≥40 U/L. Multivariate logistic regression analysis was performed to determine the association between each SUA category and elevated ALT levels in men and women, respectively. RESULTS: The prevalence of hyperuricemia and elevated ALT in men were 18.7% and 12.7%, respectively, and in women were 3.3% and 2.1%, respectively. As compared with the lowest SUA quartile, hyperuricemia was associated with elevated ALT in men (odds ratios (OR): 1.62, 95% confidence intervals (CI): 1.19-2.20) after controlling for age, service specialty, body mass index, metabolic syndrome components, current cigarette smoking, alcohol intake status, and weekly exercise times, but the associations for the other SUA quartiles were null. By contrast, the associations of hyperuricemia (OR: 0.81, 95% CI: 0.10-6.64) and the other SUA quartiles with elevated ALT were null in women. CONCLUSION: Our findings suggest that the relationship between each SUA level and elevated ALT may differ by sex among military young adults. The mechanism for the sex difference requires further investigations.

Electrocardiographic characteristics in young male patients with left primary spontaneous pneumothorax estimated by the collins equation.

OBJECTIVE: To investigate the 12-lead surface electrocardiographic (ECG) findings in young male patients with left primary spontaneous pneumothorax (PSP) estimated by the Collins equation. METHODS: From 2003 through 2008, 60 young male patients who had left PSP and 61 age-matched unaffected males were included for 12-lead ECG analyses. The PSP size was estimated by the Collins equation. Those with left PSP were divided into two groups: 1) large PSP ≥30% (n=37), and 2) small PSP <30% (n=23). The ECG in the unaffected was used as the normal control. Baseline demographic, anthropometric, and electrocardiographic findings including heart rate, P-QRS-T axes, wave intervals, and RS voltages were compared among three groups. RESULTS: As compared to the unaffected, patients with left PSP had faster heart rate, longer QTc interval, greater QRS and T axes. With regard to RS amplitudes, greater R in lead aVR and V1, and deeper S in lead II indicating predominant rightward forces, and smaller R in lead I and V3-V6 indicating inferior leftward forces were present in patients with left PSP. Of these ECG findings, heart rate, S voltage in lead II and R voltage in V1 in the large PSP but not in the small PSP had greater values than that in the unaffected group. CONCLUSION: Among young male patients with left PSP estimated by the Collins method, the ECG showed faster heart beat and predominant rightward forces especially for those with large PSP.

Chronic hepatitis B, nonalcoholic steatohepatitis and physical fitness of military males: CHIEF study.

AIM: To investigate the association of chronic hepatitis B and nonalcoholic steatohepatitis with physical fitness in a Taiwanese military male cohort. METHODS: We made a cross-sectional examination of this association using 3669 young adult military males according to cardiorespiratory fitness and hospitalization events recorded in the Taiwan Armed Forces study. Cases of chronic hepatitis B (n = 121) were defined by personal history and positive detection of hepatitis B surface antigen. Cases of nonalcoholic steatohepatitis (n = 129) were defined by alanine transaminase level > 60 U/L, liver ultrasound finding of steatosis, and absence of viral hepatitis A, B or C infection. All other study participants were defined as unaffected (n = 3419). Physical fitness was evaluated by performance in 3000-m run, 2-min sit-ups, and 2-min push-ups exercises, with all the procedures standardized by a computerized scoring system. Multiple linear regression analysis was used to determine the relationship. RESULTS: Chronic hepatitis B negatively correlated with 2-min push-up numbers (ß = -2.49, P = 0.019) after adjusting for age, service specialty, body mass index, systolic and diastolic blood pressures, current cigarette smoking, alcohol intake status, serum hemoglobin, and average weekly exercise times. Nonalcoholic steatohepatitis was borderline positively correlated with 3000-m running time (ß = 11.96, P = 0.084) and negatively correlated with 2-min sit-up numbers (ß = -1.47, P = 0.040). CONCLUSION: Chronic hepatitis B viral infection and nonalcoholic steatohepatitis affects different physical performances in young adult military males, and future study should determine the underlying mechanism.