Sex-Specific Left Ventricular and Aorta Size Cut-Off Values for Hemodynamically Significant Chronic Aortic Regurgitation　- Implications for Treatment in Asian Populations.

BACKGROUND: There are no sex-specific guidelines for chronic aortic regurgitation (AR). This retrospective study examined sex-specific differences and propose treatment criteria from an Asian AR cohort.Methods and Results: Consecutive 1,305 patients with moderate-severe AR or greater at 3 tertiary centers in Taiwan and Japan (2008-2022) were identified. Study endpoints were aortic valve surgery (AVS), all-cause death (ACD), and cardiovascular death (CVD). The median follow up was 3.9 years (interquartile range 1.3-7.1 years). Compared with men (n=968), women (n=337) were older, had more advanced symptoms, more comorbidities, larger indexed aorta size (iAortamax) and indexed left ventricular (LV) end-systolic dimension (LVESDi; P<0.001 for all). Symptomatic status was poorly correlated with the degree of LV remodeling in women (P≥0.18). Women received fewer AVS (P≤0.001) and men had better overall 10-year survival (P<0.01). Ten-year post-AVS survival (P=0.9) and the progression of LV remodeling were similar between sexes (P≥0.16). Multivariable determinants of ACD and CVD were age, advanced symptoms, iAortamax, LV ejection fraction (LVEF), LVESDi, LV end-systolic volume index (LVESVi), and Taiwanese ethnicity (all P<0.05), but not female sex (P≥0.05). AVS was associated with better survival (P<0.01). Adjusted LVEF, LVESDi, LVESVi, and iAortamaxcut-off values for ACD were 53%, 24.8 mm/m2, 44 mL/m2, and 25.5 mm/m2, respectively, in women and 52%, 23.4 mm/m2, 52 mL/m2, and 23.2 mm/m2, respectively, in men. CONCLUSIONS: Early detection and intervention using sex-specific cut-off values may improve survival in women with AR.

Costs and Cardiovascular Benefits of a Fourth-Generation Synchronous Telehealth Program on Mortality and Cardiovascular Outcomes for Patients With Atrial Fibrillation: Retrospective Cohort Study.

BACKGROUND: The prevalence of atrial fibrillation (AF) continues to increase in modern aging society. Patients with AF are at high risk for multiple adverse cardiovascular events, including heart failure, stroke, and mortality. Improved medical care is needed for patients with AF to enhance their quality of life and limit their medical resource utilization. With advances in the internet and technology, telehealth programs are now widely used in medical care. A fourth-generation telehealth program offers synchronous and continuous medical attention in response to physiological parameters measured at home. Although we have previously shown the benefits of this telehealth program for some patients with a high risk of cardiovascular disease, its benefits for patients with AF remains uncertain. OBJECTIVE: This study aims to investigate the benefits of participating in a fourth-generation telehealth program for patients with AF in relation to cardiovascular outcomes. METHODS: This was a retrospective cohort study. We retrospectively searched the medical records database of a tertiary medical center in Northern Taiwan between January 2007 and December 2017. We screened 5062 patients with cardiovascular disease and enrolled 537 patients with AF, of which 279 participated in the telehealth program and 258 did not. Bias was reduced using the inverse probability of treatment weighting adjustment based on the propensity score. Outcomes were collected and analyzed, including all-cause readmission, admission for heart failure, acute coronary syndrome, ischemic stroke, systemic embolism, bleeding events, all-cause mortality, and cardiovascular death within the follow-up period. Total medical expenses and medical costs in different departments were also compared. Subgroup analyses were conducted on ischemic stroke stratified by several subgroup variables. RESULTS: The mean follow-up period was 3.0 (SD 1.7) years for the telehealth group and 3.4 (SD 1.9) years for the control group. After inverse probability of treatment weighting adjustment, the patients in the telehealth program had significantly fewer ischemic strokes (2.0 vs 4.5 events per 100 person-years; subdistribution hazard ratio [SHR] 0.45, 95% CI 0.22-0.92) and cardiovascular deaths (2.5 vs 5.9 events per 100 person-years; SHR 0.43, 95% CI 0.18-0.99) at the follow-up. The telehealth program particularly benefited patients comorbid with vascular disease (SHR 0.11, 95% CI 0.02-0.53 vs SHR 1.16, 95% CI 0.44-3.09; P=.01 for interaction). The total medical expenses during follow-up were similar in the telehealth and control groups. CONCLUSIONS: This study demonstrated the benefits of participating in the fourth-generation telehealth program for patients with AF by significantly reducing their ischemic stroke risk while spending the same amount on medical expenses.

Correction: Effect of Telehealth Services on Mitral and Tricuspid Regurgitation Progression: Retrospective Study.

[This corrects the article DOI: 10.2196/47947.].

Effect of Telehealth Services on Mitral and Tricuspid Regurgitation Progression: Retrospective Study.

BACKGROUND: Mitral regurgitation (MR) and tricuspid regurgitation (TR) are common cardiac conditions with high mortality risks, which can be improved through early intervention. Telehealth services, which allow for remote monitoring of patient conditions, have been proven to improve the health management of chronic diseases, but the effects on MR and TR progression are unknown. OBJECTIVE: This study aimed to explore whether patients receiving telehealth services have less MR and TR progression compared with a control group. We also aimed to identify the determinants of MR and TR progression. METHODS: This single-center retrospective study conducted at the National Taiwan University Hospital compared MR and TR progression (defined as either progression to moderate or greater MR and TR or MR and TR progression by ≥2 grades during the study period) between the telehealth and control groups. Patients had a minimum of 2 transthoracic echocardiograms at least 6 months apart; baseline mild-moderate MR and TR or lower; and no prior surgeries on the mitral or tricuspid valve. Telehealth patients were defined as those who received telehealth services for at least 28 days within 3 months of baseline. Basic demographics, baseline blood pressure measurements, prescribed medication, and Charlson Comorbidity Index components were obtained for all patients. RESULTS: A total of 1081 patients (n=226 in the telehealth group and n=855 in the control group) were included in the study analyses. The telehealth group showed significantly lower baseline systolic blood pressure (P<.001), higher Charlson Comorbidity Index (P=.02), higher prevalence of prior myocardial infarction (P=.01) and heart failure (P<.001), higher beta-blocker (P=.03) and diuretic (P=.04) use, and lower nitrate use (P=.04). Both groups showed similar cardiac remodeling conditions at baseline. Telehealth was found to be neutral for both MR (hazard ratio 1.10, 95% CI 0.80-1.52; P=.52) and TR (hazard ratio 1.27, 95% CI 0.92-1.74; P=.14) progression. Determinants for moderate or greater MR progression included older age, female sex, diuretic use, larger left atrial dimension, left ventricular end-diastolic dimension, left ventricular end-systolic dimension, and lower left ventricular ejection fraction. Determinants of moderate or greater TR progression included older age, female sex, diuretic use, presence of atrial fibrillation, LA dimension, left ventricular end-systolic dimension, and lower left ventricular ejection fraction; statin use was found to be protective. CONCLUSIONS: This is the first study to assess the association between telehealth services and the progression of MR and TR. Telehealth patients, who had more comorbidities, displayed similar MR and TR progression versus control patients, indicating that telehealth may slow MR and TR progression. Determinants of MR and TR progression included easy-to-measure traditional echo parameters of cardiac function, older age, female sex, and atrial fibrillation, which can be incorporated into a telehealth platform and advanced alert system, improving patient outcomes through personalized care.

Effects of short-term oral anticoagulation following surgical bioprosthetic aortic valve replacement.

BACKGROUND: Short-term oral anticoagulation (OAC) is recommended for patients after surgical bioprosthetic aortic valve replacement (bAVR); however, the potential benefits remain controversial. This study evaluated the effects of short-term OAC following bAVR. METHODS: From 2010 to 2017, total 450 patients who underwent bAVR were enrolled. The outcomes of patients who did (OAC group) and who did not receive OAC (without-OAC group) after bAVR were compared. Propensity-score matching (PSM) was used to adjust for potential confounders, and a 1:1 matched cohort was formed. The main outcomes were all-cause mortality and bioprosthetic valve dysfunction (BVD). RESULTS: A total of 175 (39%) patients received OAC after bAVR. The median follow-up period was 2.9 years, the median duration of OAC use was 4 months; 162 pairs of patients were identified after the PSM. There was no significant difference in the prevalence of 1-year embolism/ischemic stroke between the OAC and without-OAC group in PSM cohort (0.62% vs. 1.89% for embolism, p = 0.623; 0 vs. 1.23% for ischemic stroke, p = 0.499). The prevalence of 1-year intracranial hemorrhage (ICH) between OAC and without-OAC group was also comparable (0.62% vs. 0.62%, p = 1). The OAC group had a lower all-cause mortality (adjusted hazard ratio (aHR):0.488, 95% confidence interval (CI): 0.259-0.919). There was also a trend for reduced BVD in the OAC group (aHR: 0.661, 95% CI: 0.339-1.290). CONCLUSION: Our study demonstrated that short-term OAC use after bAVR was associated with lower all-cause mortality. The prevalence of 1-year embolism/ischemic stroke/ICH were comparable despite of OAC use.

Factors associated with viral rebound among COVID-19 patients receiving oral antivirals.

BACKGROUND: COVID-19 rebound is usually reported among patients experiencing concurrent symptomatic and viral rebound. But longitudinal viral RT-PCR results from early stage to rebound of COVID-19 was less characterized. Further, identifying the factors associated with viral rebound after nirmatrelvir-ritonavir (NMV/r) and molnupiravir may expand understanding of COVID-19 rebound. METHODS: We retrospectively analyzed clinical data and sequential viral RT-PCR results from COVID-19 patients receiving oral antivirals between April and May, 2022. Viral rebound was defined by the degree of viral load increase (ΔCt ≥ 5 units). RESULTS: A total of 58 and 27 COVID-19 patients taking NMV/r and molnupiravir, respectively, were enrolled. Patients receiving NMV/r were younger, had fewer risk factors for disease progression and faster viral clearance rate compared to those receiving molnupiravr (All P < 0.05). The overall proportion of viral rebound (n = 11) was 12.9%, which was more common among patients receiving NMV/r (10 [17.2%] vs. 1 [3.7%], P = 0.16). Of them, 5 patients experienced symptomatic rebound, suggesting the proportion of COVID-19 rebound was 5.9%. The median interval to viral rebound was 5.0 (interquartile range, 2.0-8.0) days after completion of antivirals. Initial lymphopenia (<0.8 × 109/L) was associated with viral rebound among overall population (adjusted odds ratio [aOR], 5.34; 95% confidence interval [CI], 1.33-21.71), and remained significant (aOR, 4.50; 95% CI, 1.05-19.25) even when patients receiving NMV/r were considered. CONCLUSION: Our data suggest viral rebound after oral antivirals may be more commonly observed among lymphopenic individuals in the context of SARS-CoV-2 Omicron BA.2 variant.

The Impact of Synchronous Telehealth Services With a Digital Platform on Day-by-Day Home Blood Pressure Variability in Patients with Cardiovascular Diseases: Retrospective Cohort Study.

BACKGROUND: Hypertension is associated with a large global disease burden with variable control rates across different regions and races. Telehealth has recently emerged as a health care strategy for managing chronic diseases, but there are few reports regarding the effects of synchronous telehealth services on home blood pressure (BP) control and variability. OBJECTIVE: The objective of this study is to investigate the effect of synchronous telehealth services with a digital platform on home BP. METHODS: This retrospective study was conducted by the Taiwan ELEctroHEALTH study group at the Telehealth Center of the National Taiwan University Hospital. We analyzed home BP data taken from 2888 patients with cardiovascular disease (CVD) enrolled in our telehealth program between 2009 to 2017. Of the 2888 patients with CVD, 348 (12.05%) patients who received home BP surveillance for ≥56 days were selected for BP analysis. Patients were stratified into three groups: (1) poorly controlled hypertension, (2) well-controlled hypertension, and (3) nonhypertension. The mean, SD, coefficient of variation (CV), and average real variability were calculated. RESULTS: Telehealth interventions significantly and steadily reduced systolic blood pressure (SBP) in the poorly controlled hypertension group from 144.8.2±9.2 to 133.7±10.2 mmHg after 2 months (P<.001). BP variability reduced in all patients: SBP-SD decreased from 7.8±3.4 to 7.3±3.4 after 2 months (P=.004), and SBP-CV decreased from 6.3±2.5 to 5.9±2.6 after 2 months (P=.004). Event-free survival (admission) analysis stratified by SBP-SD showed longer time to first hospitalization for Q1 patients compared with Q4 patients (P=.02, odds ratio 2.15, 95% CI 1.18-3.89). CONCLUSIONS: Synchronous telehealth intervention may improve home BP control and decrease day-by-day home BP variability in patients with CVD.

Longitudinal assessment of milestone development among internal medicine residents in Taiwan.

BACKGROUND/PURPOSE: The Accreditation Council for Graduate Medical Education (ACGME) milestones have been implemented in residency training worldwide. We investigated the development of individual competency in first-year residents (R1) and second-year postgraduate students (PGY2) who received internal medicine training in Taiwan. METHODS: A multicenter observational cohort study was conducted to evaluate the competency-based milestone evaluation designed by the Taiwan Society of Internal Medicine in 2019. The evaluation was based on the ACGME-accredited milestone ratings. Periodic evaluation of milestone achievements of R1 and PGY2, who entered the internal medicine residency training at six medical centers, was performed. Each resident was evaluated every 3 months. RESULTS: Among the 98 R1 enrolled in 2019, substantial improvement in sub-competencies, including skill in performing procedures (Patient Care 4), clinical knowledge (Medical Knowledge 1), knowledge of diagnostic testing and procedures (Medical Knowledge 2), and identify impact the cost of health care and practices cost-effective care (Systems Based Practice 3) during the two years of training. Among the 107 R1 and 46 PGY2 enrolled in 2020, no significant difference in baseline milestone ratings was observed. However, the milestone assessments of R1 in 2020 showed improvement in nearly all sub-competencies compared with the stationary status of PGY2 in 2020. CONCLUSION: We demonstrate the application of ACGME-based accredited milestone ratings to target the educational goals of internal medicine residency training in Taiwan. Differences in milestone ratings between different PGY training systems exist. The long-term impact of performance among different PGY training systems requires further investigation.

Predicting the Mortality and Readmission of In-Hospital Cardiac Arrest Patients With Electronic Health Records: A Machine Learning Approach.

BACKGROUND: In-hospital cardiac arrest (IHCA) is associated with high mortality and health care costs in the recovery phase. Predicting adverse outcome events, including readmission, improves the chance for appropriate interventions and reduces health care costs. However, studies related to the early prediction of adverse events of IHCA survivors are rare. Therefore, we used a deep learning model for prediction in this study. OBJECTIVE: This study aimed to demonstrate that with the proper data set and learning strategies, we can predict the 30-day mortality and readmission of IHCA survivors based on their historical claims. METHODS: National Health Insurance Research Database claims data, including 168,693 patients who had experienced IHCA at least once and 1,569,478 clinical records, were obtained to generate a data set for outcome prediction. We predicted the 30-day mortality/readmission after each current record (ALL-mortality/ALL-readmission) and 30-day mortality/readmission after IHCA (cardiac arrest [CA]-mortality/CA-readmission). We developed a hierarchical vectorizer (HVec) deep learning model to extract patients' information and predict mortality and readmission. To embed the textual medical concepts of the clinical records into our deep learning model, we used Text2Node to compute the distributed representations of all medical concept codes as a 128-dimensional vector. Along with the patient's demographic information, our novel HVec model generated embedding vectors to hierarchically describe the health status at the record-level and patient-level. Multitask learning involving two main tasks and auxiliary tasks was proposed. As CA-mortality and CA-readmission were rare, person upsampling of patients with CA and weighting of CA records were used to improve prediction performance. RESULTS: With the multitask learning setting in the model learning process, we achieved an area under the receiver operating characteristic of 0.752 for CA-mortality, 0.711 for ALL-mortality, 0.852 for CA-readmission, and 0.889 for ALL-readmission. The area under the receiver operating characteristic was improved to 0.808 for CA-mortality and 0.862 for CA-readmission after solving the extremely imbalanced issue for CA-mortality/CA-readmission by upsampling and weighting. CONCLUSIONS: This study demonstrated the potential of predicting future outcomes for IHCA survivors by machine learning. The results showed that our proposed approach could effectively alleviate data imbalance problems and train a better model for outcome prediction.

The Costs and Cardiovascular Benefits in Patients With Peripheral Artery Disease From a Fourth-Generation Synchronous Telehealth Program: Retrospective Cohort Study.

BACKGROUND: Patients with peripheral artery disease (PAD) are at high risk for major cardiovascular events, including myocardial infarction, stroke, and hospitalization for heart failure. We have previously shown the clinical efficacy of a fourth-generation synchronous telehealth program for some patients, but the costs and cardiovascular benefits of the program for PAD patients remain unknown. OBJECTIVE: The telehealth program is now widely used by higher-risk cardiovascular patients to prevent further cardiovascular events. This study investigated whether patients with PAD would also have better cardiovascular outcomes after participating in the fourth-generation synchronous telehealth program. METHODS: This was a retrospective cohort study. We screened 5062 patients with cardiovascular diseases who were treated at National Taiwan University Hospital and then enrolled 391 patients with a diagnosis of PAD. Of these patients, 162 took part in the telehealth program, while 229 did not and thus served as control patients. Inverse probability of treatment weighting (IPTW) based on the propensity score was used to mitigate possible selection bias. Follow-up outcomes included heart failure hospitalization, acute coronary syndrome, stroke, and all-cause readmission during the 1-year follow-up period and through the last follow-up. RESULTS: The mean follow-up duration was 3.1 (SD 1.8) years for the patients who participated in the telehealth program and 3.2 (SD 1.8) for the control group. The telehealth program patients exhibited lower risk of ischemic stroke than did the control group in the first year after IPTW (0.9% vs 3.5%; hazard ratio [HR] 0.24; 95% CI 0.07-0.80). The 1-year composite endpoint of vascular accident, including acute coronary syndrome and stroke, was also significantly lower in the telehealth program group after IPTW (2.4% vs 5.2%; HR 0.46; 95% CI 0.21-0.997). At the end of the follow-up, the telehealth program group continued to exhibit a significantly lower rate of ischemic stroke than did the control group after IPTW (0.9% vs 3.5%; HR 0.52, 95% CI 0.28-0.93). Furthermore, the medical costs of the telehealth program patients were not higher than those of the control group, whether in terms of outpatient, emergency department, hospitalization, or total costs. CONCLUSIONS: The PAD patients who participated in the fourth-generation synchronous telehealth program exhibited lower risk of ischemic stroke events over both mid- and long-term follow-up periods. However, larger-scale and prospective randomized clinical trials are needed to confirm our findings.

Patient willingness to undergo a two-week free trial of a telemedicine service for coronary artery disease after coronary intervention: A mixed-methods study.

AIM: To understand the factors affecting willingness to use telemedicine in patients with coronary artery disease after coronary intervention. BACKGROUND: Telemedicine is a relatively new service provided to discharged patients in Taiwan, therefore, public acceptance is low. METHOD: This mixed-methods study conducted between January and June 2014 used convenience sampling. In total, 140 patients were offered a two-week free trial of telemedicine services before hospital discharge. Participants completed structured questionnaires and answered semi-structured qualitative questions related to willingness to use telemedicine services. RESULTS: Patients' willingness to use telemedicine was not significantly correlated with experience using technology, perceived ease of use or computer self-efficacy; instead, it was based on trust in the hospital staff, opinions of the staff and ongoing support from the case manager. Reasons for their lack of willingness to use the service were mainly related to diseases, technology/equipment and environmental factors. CONCLUSION: Staff support through telephonic tracking and real-time feedback can increase willingness to use telemedicine. IMPLICATIONS FOR NURSING MANAGEMENT: Case managers can collect necessary personal information and offer the patients 24-hr services as a monitor, an instructor and a companion, thereby accommodating more patients, building value and strengthening telemedicine services.

Use of the CHA2DS2-VASc Score for Risk Stratification of Hospital Admissions Among Patients With Cardiovascular Diseases Receiving a Fourth-Generation Synchronous Telehealth Program: Retrospective Cohort Study.

BACKGROUND: Telehealth programs are generally diverse in approaching patients, from traditional telephone calling and texting message and to the latest fourth-generation synchronous program. The predefined outcomes are also different, including hypertension control, lipid lowering, cardiovascular outcomes, and mortality. In previous studies, the telehealth program showed both positive and negative results, providing mixed and confusing clinical outcomes. A comprehensive and integrated approach is needed to determine which patients benefit from the program in order to improve clinical outcomes. OBJECTIVE: The CHA2DS2-VASc (congestive heart failure, hypertension, age >75 years [doubled], type 2 diabetes mellitus, previous stroke, transient ischemic attack or thromboembolism [doubled], vascular disease, age of 65-75 years, and sex) score has been widely used for the prediction of stroke in patients with atrial fibrillation. This study investigated the CHA2DS2-VASc score to stratify patients with cardiovascular diseases receiving a fourth-generation synchronous telehealth program. METHODS: This was a retrospective cohort study. We recruited patients with cardiovascular disease who received the fourth-generation synchronous telehealth program at the National Taiwan University Hospital between October 2012 and June 2015. We enrolled 431 patients who had joined a telehealth program and compared them to 1549 control patients. Risk of cardiovascular hospitalization was estimated with Kaplan-Meier curves. The CHA2DS2-VASc score was used as the composite parameter to stratify the severity of patients' conditions. The association between baseline characteristics and clinical outcomes was assessed via the Cox proportional hazard model. RESULTS: The mean follow-up duration was 886.1 (SD 531.0) days in patients receiving the fourth-generation synchronous telehealth program and 707.1 (SD 431.4) days in the control group (P<.001). The telehealth group had more comorbidities at baseline than the control group. Higher CHA2DS2-VASc scores (≥4) were associated with a lower estimated rate of remaining free from cardiovascular hospitalization (46.5% vs 54.8%, log-rank P=.003). Patients with CHA2DS2-VASc scores ≥4 receiving the telehealth program were less likely to be admitted for cardiovascular disease than patients not receiving the program. (61.5% vs 41.8%, log-rank P=.01). The telehealth program remained a significant prognostic factor after multivariable Cox analysis in patients with CHA2DS2-VASc scores ≥4 (hazard ratio=0.36 [CI 0.22-0.62], P<.001). CONCLUSIONS: A higher CHA2DS2-VASc score was associated with a higher risk of cardiovascular admissions. Patients accepting the fourth-generation telehealth program with CHA2DS2-VASc scores ≥4 benefit most by remaining free from cardiovascular hospitalization.

Assessment of the Relationship Between Ambient Temperature and Home Blood Pressure in Patients From a Web-Based Synchronous Telehealth Care Program: Retrospective Study.

BACKGROUND: Decreased ambient temperature significantly increases office blood pressure, but few studies have evaluated the effect of ambient temperature on home blood pressure. OBJECTIVE: We aimed to investigate the relationship between short-term ambient temperature exposure and home blood pressure. METHODS: We recruited patients with chronic cardiovascular diseases from a telehealth care program at a university-affiliated hospital. Blood pressure was measured at home by patients or their caregivers. We obtained hourly meteorological data for Taipei (temperature, relative humidity, and wind speed) for the same time period from the Central Weather Bureau, Taiwan. RESULTS: From 2009 to 2013, we enrolled a total of 253 patients. Mean patient age was 70.28 (SD 13.79) years, and 66.0% (167/253) of patients were male. We collected a total of 110,715 home blood pressure measurements. Ambient temperature had a negative linear effect on all 3 home blood pressure parameters after adjusting for demographic and clinical factors and antihypertensive agents. A 1°C decrease was associated with a 0.5492-mm Hg increase in mean blood pressure, a 0.6841-mm Hg increase in systolic blood pressure, and a 0.2709-mm Hg increase in diastolic blood pressure. This temperature effect on home blood pressure was less prominent in patients with diabetes or hypertension. Antihypertensive agents modified this negative effect of temperature on home blood pressure to some extent, and angiotensin receptor blockers had the most favorable results. CONCLUSIONS: Short-term exposure to low ambient temperature significantly increased home blood pressure in patients with chronic cardiovascular diseases. Antihypertensive agents may modify this effect.

Effect of Contract Compliance Rate to a Fourth-Generation Telehealth Program on the Risk of Hospitalization in Patients With Chronic Kidney Disease: Retrospective Cohort Study.

BACKGROUND: Chronic kidney disease (CKD) is prevalent in Taiwan and it is associated with high all-cause mortality. We have shown in a previous paper that a fourth-generation telehealth program is associated with lower all-cause mortality compared to usual care with a hazard ratio of 0.866 (95% CI 0.837-0.896). OBJECTIVE: This study aimed to evaluate the effect of renal function status on hospitalization among patients receiving this program and to evaluate the relationship between contract compliance rate to the program and risk of hospitalization in patients with CKD. METHODS: We retrospectively analyzed 715 patients receiving the telehealth care program. Contract compliance rate was defined as the percentage of days covered by the telehealth service before hospitalization. Patients were stratified into three groups according to renal function status: (1) normal renal function, (2) CKD, or (3) end-stage renal disease (ESRD) and on maintenance dialysis. The outcome measurements were first cardiovascular and all-cause hospitalizations. The association between contract compliance rate, renal function status, and hospitalization risk was analyzed with a Cox proportional hazards model with time-dependent covariates. RESULTS: The median follow-up duration was 694 days (IQR 338-1163). Contract compliance rate had a triphasic relationship with cardiovascular and all-cause hospitalizations. Patients with low or very high contract compliance rates were associated with a higher risk of hospitalization. Patients with CKD or ESRD were also associated with a higher risk of hospitalization. Moreover, we observed a significant interaction between the effects of renal function status and contract compliance rate on the risk of hospitalization: patients with ESRD, who were on dialysis, had an increased risk of hospitalization at a lower contract compliance rate, compared with patients with normal renal function or CKD. CONCLUSIONS: Our study showed that there was a triphasic relationship between contract compliance rate to the telehealth program and risk of hospitalization. Renal function status was associated with risk of hospitalization among these patients, and there was a significant interaction with contract compliance rate.

Mortality Benefit of a Fourth-Generation Synchronous Telehealth Program for the Management of Chronic Cardiovascular Disease: A Longitudinal Study.

BACKGROUND: We have shown that a fourth-generation telehealth program that analyzes and responds synchronously to data transferred from patients is associated with fewer hospitalizations and lower medical costs. Whether a fourth-generation telehealth program can reduce all-cause mortality has not yet been reported for patients with chronic cardiovascular disease. OBJECTIVE: We conducted a clinical epidemiology study retrospectively to determine whether a fourth-generation telehealth program can reduce all-cause mortality for patients with chronic cardiovascular disease. METHODS: We enrolled 576 patients who had joined a telehealth program and compared them with 1178 control patients. A Cox proportional hazards model was fitted to analyze the impact of risk predictors on all-cause mortality. The model adjusted for age, sex, and chronic comorbidities. RESULTS: There were 53 (9.3%) deaths in the telehealth group and 136 (11.54%) deaths in the control group. We found that the telehealth program violated the proportional hazards assumption by the Schoenfeld residual test. Thus, we fitted a Cox regression model with time-varying covariates. The results showed an estimated hazard ratio (HR) of 0.866 (95% CI 0.837-0.896, P<.001; number needed to treat at 1 year=55.6, 95% CI 43.2-75.7 based on HR of telehealth program) for the telehealth program on all-cause mortality after adjusting for age, sex, and comorbidities. The time-varying interaction term in this analysis showed that the beneficial effect of telehealth would increase over time. CONCLUSIONS: The results suggest that our fourth-generation telehealth program is associated with less all-cause mortality compared with usual care after adjusting for chronic comorbidities.

Complexity of heart rate variability predicts outcome in intensive care unit admitted patients with acute stroke .

BACKGROUND: Heart rate variability (HRV) has been proposed as a predictor of acute stroke outcome. This study aimed to evaluate the predictive value of a novel non-linear method for analysis of HRV, multiscale entropy (MSE) and outcome of patients with acute stroke who had been admitted to the intensive care unit (ICU). METHODS: The MSE of HRV was analysed from 1 h continuous ECG signals in ICU-admitted patients with acute stroke and controls. The complexity index was defined as the area under the MSE curve (scale 1-20). A favourable outcome was defined as modified Rankin scale 0-2 at 3 months after stroke. RESULTS: The trends of MSE curves in patients with atrial fibrillation (AF) (n=77) were apparently different from those in patients with non-AF stroke (n=150) and controls (n=60). In addition, the values of complexity index were significantly lower in the patients with non-AF stroke than in the controls (25.8±.3 vs. 32.3±4.3, p<0.001). After adjustment for clinical variables, patients without AF who had a favourable outcome were significantly related to higher complexity index values (OR=1.15, 95% CI 1.07 to 1.25, p<0.001). Importantly, the area under the receiver operating characteristic curve for predicting a favourable outcome of patients with non-AF stroke from clinical parameters was 0.858 (95% CI 0.797 to 0.919) and significantly improved to 0.903 (95% CI 0.853 to 0.954) after adding on the parameter of complexity index values (p=0.020). CONCLUSIONS: In ICU-admitted patients with acute stroke, early assessment of the complexity of HRV by MSE can help in predicting outcomes in patients without AF.

The Association between Glomerular Hyperfiltration and Left Ventricular Structure and Function in Patients with Primary Aldosteronism.

BACKGROUND: Glomerular hyperfiltration has been recently noticed as an important issue in primary aldosteronism (PA) patients. However, its effect on the cardiovascular system remains unknown. METHODS: We prospectively analyzed 47 PA patients including 11 PA patients with estimated glomerular filtration rate (eGFR) > 130 ml/min per 1.73 m2 (group 1), and 36 PA patients with eGFR 90-110 ml/min per 1.73 m2 (group 2). Fourteen essential hypertension (EH) patients with eGFR 90-110 ml/min per 1.73 m2 were included as the control group (group 3). Echocardiography including left ventricular mass index (LVMI) measurement and tissue Doppler imaging (TDI) was performed. Predicted left ventricular mass (LVM) was calculated. Inappropriate LVM was defined as an excess of > 35% from the predicted value. RESULTS: The value of LVMI decreased significantly in order from groups 1 to 3 (group 1>2>3). While group 2 had a significantly higher percentage of inappropriate LVM than group 3, the percentage of inappropriate LVM were comparable in groups 1 and 2. Group 1 had a higher mitral E velocity, E/A ratio than that of group 2. In the TDI study, the E/E' ratio also decreased significantly in order from groups 1 to 3 (group 1>2>3). Group 2 had lower E' than that of group 3, although the E' of group 1 and 2 were comparable. CONCLUSIONS: Although PA patients with glomerular hyperfiltration were associated with higher LVMI, higher mitral E velocity, higher E/E' ratio, they had comparable E' with PA patients with normal GFR. This phenomenon may be explained by higher intravascular volume in this patient group.

Multi-scale symbolic entropy analysis provides prognostic prediction in patients receiving extracorporeal life support.

INTRODUCTION: Extracorporeal life support (ECLS) can temporarily support cardiopulmonary function, and is occasionally used in resuscitation. Multi-scale entropy (MSE) derived from heart rate variability (HRV) is a powerful tool in outcome prediction of patients with cardiovascular diseases. Multi-scale symbolic entropy analysis (MSsE), a new method derived from MSE, mitigates the effect of arrhythmia on analysis. The objective is to evaluate the prognostic value of MSsE in patients receiving ECLS. The primary outcome is death or urgent transplantation during the index admission. METHODS: Fifty-seven patients receiving ECLS less than 24 hours and 23 control subjects were enrolled. Digital 24-hour Holter electrocardiograms were recorded and three MSsE parameters (slope 5, Area 6-20, Area 6-40) associated with the multiscale correlation and complexity of heart beat fluctuation were calculated. RESULTS: Patients receiving ECLS had significantly lower value of slope 5, area 6 to 20, and area 6 to 40 than control subjects. During the follow-up period, 29 patients met primary outcome. Age, slope 5, Area 6 to 20, Area 6 to 40, acute physiology and chronic health evaluation II score, multiple organ dysfunction score (MODS), logistic organ dysfunction score (LODS), and myocardial infarction history were significantly associated with primary outcome. Slope 5 showed the greatest discriminatory power. In a net reclassification improvement model, slope 5 significantly improved the predictive power of LODS; Area 6 to 20 and Area 6 to 40 significantly improved the predictive power in MODS. In an integrated discrimination improvement model, slope 5 added significantly to the prediction power of each clinical parameter. Area 6 to 20 and Area 6 to 40 significantly improved the predictive power in sequential organ failure assessment. CONCLUSIONS: MSsE provides additional prognostic information in patients receiving ECLS.

The arrhythmogenic effect of self-assembling nanopeptide hydrogel scaffolds on neonatal mouse cardiomyocytes.

The chaotic spatial disarray due to extracellular matrix expansion disrupts cardiomyocytes interaction and causes arrhythmia. We hypothesized that disordered nanopeptide scaffolds can mimic the chaotic spatial disarray related to cardiac fibrosis and have arrhythmogenic effects on cardiomyocytes. Primary mouse cardiomyocytes were cultured in 2D traditional and 3D nanopeptide hydrogel scaffold systems. Cardiomyocytes in 3D scaffolds showed irregular spontaneous contractile activity as compared with 2D culture controls. Calcium fluorimetric imaging revealed that basal intracellular calcium level increased 1.42-fold in cardiomyocytes cultured in the 3D scaffold, in vitro. The mRNA levels of sarcoplasmic reticulum calcium transport ATPase, ryanodine 2 receptor and connexin 43 elevated 2.14-fold, 2.33-fold and 2.62-fold in 3D compared with 2D. Immunofluorescence imaging revealed lateralization of the distribution of connexin 43 in 3D group. These findings suggest that 3D hydrogel culture system provides a model for the development of cardiac dysrhythmia. These limitations should be considered during cardiac tissue engineering. FROM THE CLINICAL EDITOR: This team of scientists has established a unique 3D hydrogel culture system as a model for the development of cardiac dysrhythmia.