bluuebunny/crossref_metadata_2025 huggingface dataset:
Biventricular modelling for investigating ventricular arrhythmias in silico
Authors: Cheng F , Rauseo E , Misghina S , Barrera C , Vigmond E , Slabaugh G , Aung N , Petersen S , Roney C
Published: October 2024

Background

Ventricular arrhythmias have a significant incidence rate worldwide and may potentially lead to sudden cardiac death in severe cases. Despite therapeutic advancements, the intricate mechanisms dictating these arrhythmias remain elusive. Biventricular modelling and deep learning provide a way to investigate the complex electrophysiological substrates underlying cardiac arrhythmogenesis.

Purpose

This study aims to develop and validate a patient-specific biventricular computational modelling pipeline for simulating ventricular arrhythmias in silico. We provide a comprehensive platform for understanding the initiation, propagation, and treatment response of various ventricular arrhythmias.

Methods

To facilitate large-scale computational experiments and personalised model predictions within clinical timeframes, it is imperative to establish a rapid and reproducible modelling framework. First, we constructed biventricular volumetric models derived from late gadolinium-enhanced magnetic resonance imaging (LGE-MRI) data from the Cardiac Atlas Project (2018 Atria Segmentation Challenge), and then we calculate biventricular coordinates to facilitate data registration between measures, and fibre and fibrosis inclusion. We also apply the pipeline to cardiac magnetic resonance (CMR) data and electrocardiogram recordings from UK Biobank.

Results

We have successfully developed a pipeline for constructing biventricular volumetric models and efficiently processed biventricular coordinates (Figure). By systematically exploring interactions between ventricular regions, the model may identify critical factors contributing to arrhythmia susceptibility and guide personalised therapeutic strategies. Furthermore, the model may provide insights into the efficacy of antiarrhythmic interventions, ablation techniques, and device therapies, facilitating the development of precision medicine approaches.

Conclusions

We demonstrate a pipeline for constructing patient-specific biventricular computational models at scale from imaging data and apply this to LGE-MRI data and UK Biobank CMR data. These biventricular models enable investigation of the complex mechanisms of ventricular arrhythmias, providing novel insights for clinical decision-making and treatment strategies.
Initial experience with a 5G cellular network and robotic arm-based remote echocardiographic system in an all-comers setting
Authors: Liu Y , Meng F , Zhou N , Wu Y , Hu C , Fang X , Chen H , Pan C , Shu X , Ge J
Published: October 2024

Background

Echocardiography is the test-of-choice for the initial evaluation of many cardiac diseases and requires expertise that is often limited in rural area. Robotic arm-assisted remote echocardigram has been attampted for teleconsultation but was limited to heart failure patients(ref), primarily due to the network delay in telecommunication and the subsequent incoordination in robotic arm control.

Purpose

We aim to assess the feasibility and diagnostic accuracy of a 5G cellular network and robotic arm-based remote echocardiographic system in an all-comers setting.

Methods

51 pts were enrolled from the outpatient cardiology clinic of our institute. All pts underwent standard comprehensive echocardiography on a 5G cellular network and robotic arm-based remote echocardiographic system (the robotic part was deployed at our hospital and the control part was located at another campus 20 kilometers away) (Figure 1)and a conventional echocardiographic platform (at our hospital) successively. The order in which patients were examined on the remote and conventional instruments was randomly determined. There was no interval between the two examinations, and examinations of the same patient were performed by experienced but different cardiologists, who were blinded to each other’s diagnosis. The doctor who used the remote system was also randomly allocated and had not been previously specifically trained. The exams were real-time and diagnoses were made right after the exams.

Results

Of the 51 pts, the image quality was sufficient for diagnosis in 50 patients (48% female, 40±18 years). 1 pt was excluded because some key views could not be obtained using the remote system (98% of exams successful). 17 pts had positive findings, including 10 with a primary diagnosis of valvulopathy (1 Barlow's syndrome, 1 bicuspid aortic valve and 8 less-than-moderate regurgitation), 2 cardiac surgery follow-ups (1 case of aortic valve replacement and septal myectomy, and 1 case of mitral valve replacement and tricuspid annuloplasty), and 2 hypertrophic cardiomyopathy (including 1 case of obstruction at papillary muscle level), 2 with abnormal left ventricular wall motion(including 1 case of apical mural thrombus) (Figure 2), and 1 with congenital heart disease (secumdum atrial septal defect). The main diagnosis was consistent in 98% of cases (papillary muscle level obstruction was missed in one case), using conventional echocardiographic findings as the standard. Time for image acquision using remote echocardiography was significantly longer than conventional one (24 minutes 36 seconds ± 4 minutes 52 seconds vs. 16 minutes 15 seconds ± 1 minute 54 seconds, p<0.0001, paired t-test).

Conclusions

Comprehensive echocardiographic exam with a 5G cellular network and robotic arm-based remote system is feasible with relatively good diagnostic accuracy.Figure 1Figure 2
The cost-effectiveness of a digitally enabled telerehabilitation program delivered nationally to patients in Australia
Authors: Braver J , Salim A , Oldenburg B , Carrington M J , Marwick T
Published: October 2024

Introduction

Traditionally delivered cardiac rehabilitation (CR) programs have considerable benefits, yet access and participation remains low. Emerging digital health models offer promise in healthcare delivery, but their benefits and impact on healthcare utilization and cost-effectiveness are uncertain. We conducted a cost-effectiveness analysis of a telehealth program with a CR mobile app for post-hospitalization coronary heart disease (CHD) patients.

Purpose

To assess whether a digitally enabled CR program is cost-effective compared with a propensity matched usual care control group in the Australian health system.

Methods

Patients were recruited nationally, through a health insurer, following hospitalization for CHD. Participants received weekly telehealth consultations for up to 8 weeks, supplemented by use of an mHealth app. Using administrative private health insurance claims data, we assessed differences in hospital costs, mortality rates and bed days at 12-months post discharge. Incremental cost effectiveness ratios (ICERS) were calculated to determine the cost per deaths prevented and cost per bed days saved for the digital-CR group (n=133) compared with usual care (n=266).

Results

Among the cohort, 36% lived in regional/rural areas, 70% were male and the mean age was 68 years. The mean total hospital all cause readmission costs at 12-months were $1,488 AUD less in the digital-CR group ($16,411) compared to the usual care group ($17,899). Digital-CR had fewer total hospital days relative to the usual care group (median of 2 vs 3 days) and patients in the digital-CR group had a significantly lower mortality rate at 12-months post discharge. The ICERs were -$337 per 100 patient deaths prevented and -$3,033 per median bed days saved.

Conclusion

The implementation of a digital-CR program demonstrates cost-effectiveness for patients with CHD when compared to usual care. Thus, advocating for the widespread availability of digital-CR programs as an option for CHD patients following hospital discharge is warranted.
Digital literacy of patients with chronic heart failure using telemedicine in france: a national observational cohort study
Authors: Girerd N , Jourdain P , Hanon O , Jagu A , Seronde M F , Tartiere J M , Amara W , Benchimol H , Albert F , Abdenhader M , Nisse-Durgeat S , Pages N , Picard F
Published: October 2024

Introduction

Remote patient monitoring (RPM) is increasingly considered for chronic care management. However, several challenges exist for its implementation such as funding resources, lack of standardizations and gaps in digital literacy.

Objective

The aim of this study was to describe patients using RPM to manage chronic heart failure (CHF) according to their digital literacy at a national scale in France.

Methods

A national retrospective study was conducted using a remote monitoring system for the management and therapeutic guidance of patients with CHF. Patients were categorized according to their digital literacy (digitally literate vs poor digital literacy). The latter were identified as requiring nurse assistance in medical data entry. Data collection included baseline characteristics, comorbidities, RPM status, heart failure-related hospitalizations and mortality.

Results

Of the 12,072 patients with CHF enrolled for RPM follow-ups (male: 65.4%, mean age: 74.2±13.1 years), 43.3% had poor digital literacy. These patients were older (79.4±10.2 vs 70.2±13.6 years) and were less among males (39.7% vs 60.3%). Overall, digitally literate patients had more comorbidities, including diabetes (61.8%) and obesity (69.4%). Over a third of all patients withdrew from RPM (37.0%). Continued use of RPM was higher in digitally literate patients (60.1% vs 39.9%, p<0.001). Mortality was higher in patients with poor digital literacy (OR: 0.71, 95%CI: 0.66 to 0.78, p<0.0001). Poor digital literacy was linked to increased occurrences of HF episodes in contrast to digitally literate patients (34.1% vs 25.8%) who had an uHR of 0.66 (95%CI: 0.62 to 0.71, p<0.0001), and an aHR of 0.68 (95%CI: 0.64 to 0.73, p<0.0001).

Conclusion

Patients with poor digital literacy form a sizable subgroup in heart failure management and may require specialized tools tailored to their needs. Prevalence of poor digital literacy may increase the risk of HF hospitalization and mortality and reduce RPM adherence.
Effect of remote monitoring on the management of heart failure patients with cardiac amyloidosis
Authors: Mouhat B , Seronde M F , Jagu A , Esser R , Becle C , Nisse-Durgeat S , Pages N , Picard F
Published: October 2024

Objective

The primary objective was to assess the characteristics of heart failure (HF) patients with cardiac amyloidosis (CA) monitored remotely with our program. The secondary objective was to evaluate the discrimination of alerts by remote monitoring for HF in this specific population.

Methods

The entire multicentre cohort of HF patients monitored remotely with our program from August 2018 to December 2023 were included in the analysis.

Results

A total of 13,933 patients, including 346 (2.5%) with CA and 13,587 (97.5%) without cardiac amyloidosis (no-CA), had a median follow-up of 14 months. CA patients were more often male (78.6% vs 63.8%), over 80 years of age (69.9% vs 40.4%), with left ventricular ejection fraction >40% (78.6% vs 56.5%), more often NYHA class III-IV (26.6% vs 16.2%), more atrial fibrillation (54.0% vs 40.9%) but less myocardial infarction (8.4% vs 27.9%), diabetes (16.5% vs 28.1%), smoking (2.9% vs 13.4%), p<0.001 for all. There was no difference in the rate of renal failure (21.7% vs. 20.3%), obstructive sleep apnea (15.9% vs. 14.9%) or stroke (10.7% vs. 9.4%). Remote monitoring identified a total of 57,624 alerts, including 1240 in the CA group vs 56,384 in the no-CA group (i.e. 3.58 alerts per CA patient vs 4.15 alerts per no-CA patient). Of the alert resolutions in the CA group vs no-CA group, 22.4% vs 38.9% had a low probability of cardiac decompensation, 34.0% vs 35.4% had a moderate probability, 43.6% vs 25.7% had a high probability of cardiac decompensation (global Chi-square p<0.001).

Conclusion

Despite an elderly population with different comorbidities, remote monitoring with this program in CA patients identifies correct relevance for discrimination of cardiac decompensation.
Measurement inaccuracy reported via the Manufacturer and User Facility Device Experience database for an implantable pulmonary artery pressure sensor: recalibration direction and magnitude results
Authors: Wetterling F , Kittipibul V , Fudim M
Published: October 2024

Introduction

Remote monitoring using an implantable pulmonary artery pressure (PAP) sensor (CardioMEMS HF system) in patients with heart failure (HF) has been consistently shown to reduce HF hospitalizations [1]. The success of this approach relies on the accurate measurement of diastolic PAP (dPAP) over time to allow early interventions such as diuretic intensification [2]. However, it remains unclear how the measurement accuracy changes over time after the initial calibration at the time of device implantation.

Purpose

This study aims to identify measurement inaccuracy events and to quantify the magnitude and direction of required device recalibration for CardioMEMS devices as reported in a large-scale regulatory device database.

Methods

We used the publicly accessible Manufacturer and User Facility Device Experience (MAUDE) data maintained by the US Food and Drug Administration (FDA). The summary search was performed for the CardioMEMS pulmonary artery pressure sensor for the entire product life cycle from January 2009 to February 2024 [3,4]. The entries related to the measurement accuracy under ‘Device Problems’ categories were obtained. Tested accuracy was reported to have been within ±10mmHg of a reference pressure measurement throughout simulated use for 10 years [5]. Normal range for dPAP is ~8mmHg to 15mmHg [6].

Results

A total of 2656 entries were obtained. Following categories were identified for the reported entries: device sensing problem (N=999, 38%); incorrect measurement (N=1349, 52%); incorrect measurement, inappropriate waveform (N=279, 11%), and incorrect, inadequate, or imprecise results or readings (N=29, 1%). After excluding 56 entries for missing information, 2600 entries were included for the analysis. A total of 1676 (64%) entries reported the need for recalibration of the CardioMEMS device. A mean PAP difference (defined as the difference of the mean PAP reference value measured at the time of recalibration minus the CardioMEMS reading obtained during the reference measurement) is shown in Figure 1. Compared to the reference pressure values at the time of recalibration, 488 (29%) of CardioMEMS readings were higher and 1188 (71%) were lower. The absolute recalibration pressure difference was 14.5 ± 9.3 mmHg (mean ± standard deviation, range 0.02-59.3 mmHg). The recalibration by more than 10 mmHg was reported in 1040 (40%) entries.

Conclusions

Suspected measurement inaccuracy with CardioMEMS device is not uncommon and often necessitate recalibration. Almost one-half (40%) of the recalibrations required more than 10 mmHg correction. These results should inform clinicians to consider recalibration along the course of CardioMEMS monitoring if there is discordance between clinical assessment and the values from the device.Figure 1.Figure 2
Quality of life in atrial fibrillation patients and its relationship to family member anxiety and depression
Authors: Tao L , Zhang X H , Song H Y , Li S H , Zhang Z H
Published: October 2024

Background

Atrial fibrillation (AF) has been found to decrease quality of life (QOL), and a few studies suggest that family members of AF patients can also experience negative emotions. This study aims to assess the anxiety and depression of the immediate family members of AF patients and to investigate the influence of the QOL of the AF patients on this anxiety and depression.

Method

This cross-sectional study recruited 121 pairs of AF patients and their immediate relatives along with 121 controls who and whose immediate relatives did not have AF. The patients filled out the Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) questionnaire, and the relatives and the controls were required to complete the State-Trait Anxiety Inventory (ST-AI) and Self-Rating Depression Scale (SDS).

Results

The score (mean (SD)) of the State Anxiety Inventory (S-AI, a subscale of ST-AI) in the relatives’ group was 44.9 (10.6), which was significantly higher than that of the control group (38.5 (9.5), p < 0.001). Among the different kinship subgroups, the children of the AF patients had the highest state anxiety score (mean value = 47.0, p=0.075). A negative linear relationship between the patients' overall AFEQT score and the relatives' S-AI score was found (standardized regression coefficient = -0.244, p < 0.001). For those patients who had particularly low AFEQT scores of less than 40, their relatives’ S-AI scores were significantly higher than other members of the relatives’ group (52.1 vs. 42.9, p = 0.001). AF patients in the peri-ablation period (81, 66.9%) had no difference in their AFEQT scores compared to other patients (60.8 vs. 64.4, p= 0.316) and there was also no difference in their family members’ ST-AI or SDS scores.

Conclusion

Study members showed considerable state anxiety if their family members had AF and increases in this anxiety were positively correlated with decreases in the HRQOL of the AF patients.
Weekend compensatory sleep is associated with reduced risk of heart disease: a prospective UK Biobank-based cohort study
Authors: Liu Z , Song Y J
Published: October 2024

Background and Aims

Influenced by the demands of school or work, people often fall out of sync with their circadian rhythms, which leads to sleeping in on days off. Despite this phenomenon, there is a lack of research examining whether compensatory weekend sleep has positive effects on heart health.

Methods and results

Our prospective cohort study utilized data from the UK Biobank (UKB) and encompassed 90,903 participants. To evaluate the relationship between compensated weekend sleep and heart disease. The sleep data was recorded by Axivity AX3 accelerometer from UKB and grouped by quartiles. Hospitalization records and cause of death registry information were used to diagnose various cardiac diseases including IHD, HF, AF, and stroke. Then multivariate Cox proportional hazard modeling was used to examine the potential impact of compensated sleep on the risk of heart disease.

At a median follow-up time of up to 13.8 years, we found that participants in the compensatory sleep group(Q4) had a lower risk of having heart disease in the fully adjusted model (HR: 0.809, 95%CI: 0.766,0.854), which was not influenced by the effect of genetic risk for IHD, HF, or AF. These relationships were even more pronounced in the subgroup with daily sleep deprivation (HR:0.801, 95%CI: 0.718,0.894).

Conclusion

Sufficient compensatory sleep on weekends is linked to a low risk of heart disease, including IHD, AF, HF, and stroke, which is independent of genetic risk. And the association becomes even more pronounced among individuals who regularly experience inadequate sleep on weekdays.Visual abstract
Association between adherence to LS7 and frailty among older US adults
Authors: Wu S , Yang Y , Zhu J
Published: October 2024

Objective

The Life's Simple 7 (LS7) metrics were developed by the American Heart Association to define ideal cardiovascular health. The impact of LS7 on frailty among older adults remains unclear. Our objective was to examine the association between the cardiovascular health score and risk of frailty among older adults.

Designs, Settings, and Participants

Data from the National Health and Nutrition Examination Surveys (NHANES) 1999-2018 was used. We included 9242 community-dwelling adults aged ≥ 65 years. The LS7 score was calculated for all participants. Frailty was measured with the 40-item frailty index, and a frailty index score of > 0.21 was defined as ‘frailty’. Log-binominal regression and negative binomial regression were conducted to estimate the association between LS7 and frailty. Mediation analysis was used to estimate the mediating effects of inflammatory indicators on the association.

Results

The weighted average of frailty index score was 0.18, and 3206 participants (34.8%) were identified as ‘frailty’. Participants with high LS7 scores had significantly lower frailty index score and prevalence of frailty than those with low LS7 scores. In fully adjusted log-binominal regression models, with total score < 6 as a reference, the ORs (95% CIs) for frailty were 0.79 (0.65, 0.96), 0.66 (0.54, 0.80), 0.50 (0.39, 0.65), and 0.39 (0.29, 0.52) for total score = 6, total score = 7, total score = 8, and total score > 8, respectively. When LS7 score analyzed as a continuous variable, per 1-point increase in the LS7 score was associated with a 16% decrease in the risk of frailty (P < 0.001). In negative binominal regression models, the adjusted PRs (95% CIs) for frailty were 0.96 (0.93, 1.00), 0.94 (0.91, 0.97), 0.91 (0.87, 0.95), and 0.85 (0.82, 0.88) for total score = 6, total score = 7, total score = 8, and total score > 8, respectively. For each 1-point increase in the LS7 score, the risk of frailty decreased by 3% (P < 0.001). No significant interactions were observed in subgroups stratified by age, sex, race, body mass index, smoking status, alcohol consumption, and self-reported health status. Causal mediation analysis indicated that inflammatory factors including blood cell count, neutrophil count, and C-reactive protein positively mediated the association of LS7 with frailty, with a mediating proportion of 0.0357 (P = 0.01), 0.0741 (P < 0.001), and 0.0524 (P = 0.012), respectively.

Conclusions

In a nationally representative sample of U.S. adults, increased exposure to EO was independently related to an increased prevalence of frailty.Association between LS7 and frailtySubgroup analysis
The association between the dietary salt intake and glucose intolerance in healthy populations: from the Korean National Health and Nutritional Examination Survey (KNHANES)
Authors: Rha S , Choi B G , Choi S Y , Cha J , Hyun S , Kang J , Chu W , Park S , Choi C U , Park C G
Published: October 2024

Background

Diabetes is known to be a strong risk factor for cardiovascular disease (CVD), and controlling salt intake in patients with type 2 diabetes may be a strategy to reduce the risk of CVD. However, the clear interaction between salt intake and glucose homeostasis has yet to be investigated. Our study evaluated the frequency and risk of glucose intolerance (pre-diabetes) according to dietary salt intake in a healthy population in Korea.

Methods

The Korean National Health and Nutritional Examination Survey (KNHANES) database was utilized for this study (https://knhanes.cdc.go.kr). A total of 72,751 subjects were enrolled in the KNHANES database from 2010 to 2018. The subjects were categorized into the following: normal fasting glucose (i.e., no pre-diabetes; FPG < 100 mg/dL), stage 1 pre-diabetes (FPG 100–109 mg/dL), stage 2 pre-diabetes (FPG 110–125 mg/dL). All subjects were divided into 8-equal groups according to their sodium intake: Group 1: ≤ 3.5 g, Group 2: 3.5 to 5.0 g, Group 3: 5.0 to 6.3 g, Group 4: 6.3 to 7.8 g, Group 5: 7.8 to 9.5 g, Group 6: 9.5 to 11.8 g, Group 7: 11.8 to 15.5 g, Group 8: > 15.5 g. This study is a retrospective cross-sectional study, so future risks cannot be assessed, but only the disease status assessment at the same time.

Results

Of the total 36,782 healthy adults, 17.6% (6,481 subjects) were pre-diabetic, of which 14.7% (5,397 subjects) were stage I pre-diabetic, and 2.9% (1,084 patients) were stage II pre-diabetic. From the lowest salt intake group (group 1, salt intake <3.5g) to the highest salt intake group (group 8, salt intake>.5g), the pre-diabetes prevalence continuously increased from 9.2% to 22.8%. The range of stage 1 pre-diabetes was 7.3% to 18.3%, and stage 2 diabetes was 1.9% to 4.5%. The odds ratio (OR) of pre-diabetic risk according to salt intake in the non-diabetic population, compared with group 1, group 2 was 1.46 (95% confidence interval [CI]: 1.30-1.68), group 3 was 1.84 (95% CI: 1.62 -2.08), group 4 was 2.24 (95% CI: 1.99-2.54), group 5 was 2.43 (95% CI: 2.15-2.75), group 6 was 2.49 (95% CI: 2.20-2.81), group 7 was 2.83 (95% CI: 2.51-3.19), group 8 was 2.90 (95% CI: 2.57-3.27).

Conclusions

High salt intake is significantly associated with pre-diabetes prevalence in healthy Korean population.
Vaccination status and long COVID symptoms among patients hospitalized with COVID-19: the WHF COVID-19 Long-term Study
Authors: Singh K , Prabhakaran D , Nikhare K , Raspail L , Banerjee A , Narula J , Pineiro D , Perel P , Sliwa Hahnle K
Published: October 2024

Background

COVID-19 vaccinations have been found to be effective in reducing the severity of COVID-19 infection and in-hospital deaths; however, insufficient evidence exists about the effect of vaccination on long term morbidity and mortality after hospitalization in patients from low- and middle-income countries.

Methods

The global WHF COVID-19 Long-Term Follow-up Study recruited 2,504 COVID-19 hospitalized patients from 26 collaborating sites in 16 countries between January 2022 - June 2023. Patients were followed up , at 1, 3, 6, and 9-12 months post-discharge to examine short- and long-term physical and psycho-social outcomes. A standardised questionnaire was used to collect data on demographics, pre-existing comorbidities, COVID-19 symptoms on admission, vaccination status, and outcomes at discharge, including persisting symptoms, new onset hypertension or diabetes, major adverse cardiovascular events (MACE), and mortality. We compared persistent long COVID symptoms, MACE, and mortality outcomes up to one year by COVID-19 vaccination status.

Results

The majority of study participants were Asians (78%), males (56%) with a mean (SD) age of 59.2 (19.9) years and from low- and middle-income (65%), upper middle-income (20%) and high-income (15%) countries. The most commonly reported comorbidities were hypertension: 54% and diabetes: 38%. Approximately two-thirds of the patients had received at least one dose of COVID-19 vaccination prior to hospitalization. Unvaccinated patients were more likely to present with dyspnea (60% vs 53%, p-value<0.001) and acute respiratory infection (15% vs 9%, p-value<0.001) during hospitalization. Unvaccinated patients also had twice the in-hospital mortality rate, compared with vaccinated patients (6% vs 3%, p-value<0.001). Unvaccinated patients had a greater incidence of MACE (23% vs 18%, p-value=0.016) during hospitalization and across all follow-up visits. Unvaccinated patients also had a higher mortality rate across all follow-up visits (mortality at one year post-discharge 14% vs 10%, p<0.001). At the 9-12 month follow-up, about a quarter of the patients had at least one long COVID symptom, but unvaccinated patients had a higher rate of long COVID symptoms, including fatigue (23% vs 14%, p<0.001), palpitations (17% to 7%, p-value<0.001), and anxiety (13% to 7%, p=0.002).

Conclusions

Our data highlight the long-term protective effect of COVID-19 vaccination on reducing morbidity and mortality among COVID-19 patients after hospital discharge. However, a substantial proportion of COVID-19 vaccinated patients still showed persistent long COVID symptoms (22%) and mortality (10%). Future research is needed to investigate individual- and health system-level factors contributing to poor health outcomes post-COVID-19 infection.
All-cause, cancer and cardiovascular mortality among South Asians living in the UK: Follow-up of the London Life Sciences Population (LOLIPOP) cohort
Authors: Kooner I , Zhang W , Geoghegan F , Kooner A S , Scott J , Elliott P , Chambers J C , Kooner J S
Published: October 2024

Background

Although South Asians are the largest ethnic minority group in the UK, and the largest ethnic group worldwide, few studies have investigated patterns of mortality in South Asians.

Methods

We investigated 16,391 South Asian and 6,970 European men and women living in the UK, and participating in the London Life Sciences Prospective Population study. Participants were recruited in 2002-2008, and survival determined to 2019. We examined relationships of clinical, anthropometric, and lifestyle risk factors to mortality outcomes.

Findings: Compared to Europeans, South Asians had higher prevalence of diabetes, cardiovascular disease, and hypertension, higher waist-hip ratio, fasting glucose, insulin and triglycerides, but lower smoking rates and HDL cholesterol (all P<0.001). Age and sex adjusted all-cause mortality was lower (Hazard Ratio (HR): 0.75 [0.68-0.81], P<0.001), all-cancer mortality was lower (HR 0.50 [0.43-0.58], P<0.001), and coronary heart disease (CHD) mortality was higher (HR 1.29 [1.05-1.60], P<0.01) in South Asians compared to Europeans. Mortality rates were ~50% lower for 9 of the 10 most common cancers in South Asians. After adjusting for risk factors, ethnic differences were attenuated only for CHD mortality.

Interpretation: All-cause and cancer mortality are lower, but CHD mortality is higher, in South Asians compared to Europeans. Measured risk factors do not explain lower all-cause and all-cancer mortality, but do account for higher CHD mortality. Our findings provide evidence for population-specific exposures protective against cancers in South Asians, as well as the motivation to further improve cardiovascular risk reduction in this major ethnic group.
Short-term effects of ambient temperature variability on myocardial infarction hospitalizations in Sweden: A nationwide case-crossover study
Authors: Ni W , Stafoggia M , Zhang S , Ljungman P , Breitner S , Bont J D , Jernberg T , Atar D , Schneider A , Agewall S
Published: October 2024

Background

Climate change threatens human health and general welfare via multiple dimensions. However, the short-term effect of temperature variability, a crucial aspect of climate change, on myocardial infarction (MI) remains largely unexplored.

Purpose

We aimed to assess the short-term effects of temperature variability on MI hospitalizations within the nationwide SWEDEHEART registry.

Methods

This population-based nationwide study involved 228,897 MI patients from the SWEDEHEART registry in Sweden from 2005 to 2019. High-resolution (1 km × 1 km) daily mean ambient temperature was estimated using a spatiotemporal machine learning methodology and assigned to patients’ home addresses. Temperature variability was calculated as the difference between the same-day (as the MI event) ambient temperature and the average temperature recorded over the preceding seven days. Specifically, an upward temperature shift represents a rise in the current day’s temperature relative to the seven-day average, while a downward temperature shift indicates a corresponding decrease. A time-stratified case-crossover design incorporating a conditional logistic regression model with distributed lag non-linear model was applied to estimate the association between ambient temperature variability and total MI, ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI). Moreover, we assessed potential effect modification by sex and medication intake. The results were expressed as odds ratio (OR, with their 95% confidence intervals [CIs]) per 1°C increase in temperature variability.

Results

Our study found that a 1°C increase in upward temperature shift was significantly associated with increased risks for total MI, STEMI, and NSTEMI (OR [95% CI]: 1.010 [1.006-1.015], 1.014 [1.006-1.022], and 1.009 [1.004-1.014], respectively). Furthermore, a 1°C greater in downward temperature shift was significantly associated with decreased risks for total MI and NSTEMI (OR [95% CI]: 0.995 [0.991-0.999], and 0.993 [0.988-0.998], respectively). Moreover, we found that males and patients who were on any heart medication, particularly digitalis, were at a higher risk of MI associated with exposure to higher upward temperature shifts compared to females and their counterparts not taking these medications.

Conclusions

This nationwide case-crossover study provides novel evidence that short-term exposure to increasing upward temperature shift is associated with an increased risk of MI hospitalization. Our finding highlights the cardiovascular health threats posed by upward temperature shifts, which are anticipated to increase in frequency and intensity due to climate change.
Cost-effectiveness analysis of implementing the Nagasaki Acute Myocardial Infarction (AMI) secondary prevention clinical pathway
Authors: Kurobe M , Yamanaka Y , Uda A , Mori K , Inoue S , Yoshimura M , Ikeda S , Maemura K
Published: October 2024

Background/Introduction

Because of the poor prognosis associated with acute coronary syndromes (ACS), intensive low-density lipoprotein cholesterol (LDL-C) management therapy is recommended as early as possible after the onset of ACS, with the goal of lowering plasma LDL-C to <70 mg/dL.

In Nagasaki City, a council was formed comprising all hospitals performing percutaneous coronary intervention along with general physicians, and an initiative to manage LDL-C using a region-wide LDL-C management clinical pathway (Figure 1) was launched in July 2022. The rate of intensive statin therapy at discharge increased from 34.5% to 79.8%, and the rate of patients achieving LDL-C <70 mg/dL at discharge increased from 37.2% to 54.6% following the implementation of the clinical pathway. However, the cost-effectiveness of implementing the clinical pathway remains to be determined.

Purpose: The purpose of this study was to evaluate the cost-effectiveness of implementing the Nagasaki AMI Secondary Prevention Clinical Pathway.

Methods: To evaluate the cost-effectiveness of implementing the clinical pathway compared with no implementation, a lifetime simulation was performed using mathematical models. The models consisted of a decision tree model to model the flow of the clinical pathway (Figure 2) and a Markov model to consider the risks of developing cardiovascular disease (CVD) events. The quality-adjusted life year (QALY) was used as the outcome. Drug costs and treatment costs for each CVD event were included. Drug costs were calculated from actual prescriptions. Treatment costs and utility scores for each event were based on the literature. The risk of each CVD event was calculated using baseline risks estimated using commercial claims data (DeSC Healthcare, Inc.) and patients' LDL-C levels at discharge and 1 month after discharge. LDL-C levels at each time point were set separately for the groups that achieved or did not achieve a discharge LDL-C < 70 mg/dL, for patients with and without implementing the clinical pathway.

Results: Implementing the clinical pathway was evaluated as dominant, with an incremental gain of 0.079 QALYs per person and expected cost savings of JPY 103,124 per person. Implementing the clinical pathway was shown to not only provide additional health benefits by preventing CVD, but also to reduce future health care costs. In the analysis with a 10-year time horizon, the result remained dominant, and the same level of cost savings was expected.

Conclusions: Implementing the Nagasaki AMI Secondary Prevention Clinical Pathway can be expected to reduce costs, in addition to increasing QALYs by preventing CVD. Further clinical and economic evaluation of long-term follow-up with a collaborative pathway to the general physician after discharge from the hospital is expected.
The Waiting 4 Surgery study: burden of in-hospital care
Authors: Campos I , Oliveira I , Lopes R G , Braganca B , Cruz I , Monteiro J P , Goncalves I , Andrade A
Published: October 2024

Introduction

Patients with coronary artery and valvular diseases with surgical indication represent a significant proportion of hospitalizations. The Waiting 4 Surgery study (W4S) aims to better study this group of patients, their burden of hospital care and identify those with event-free admissions.

Purpose

In this work, we analyze both the economical and hospital-care burden of this group of patients.

Methods

Retrospective study of consecutive patients admitted between 2019 and 2021 with coronary artery and/or aortic valve diseases waiting for coronary artery bypass graft (CABG), aortic valve replacement (AVR; surgical or percutaneous) or both. Total admission time and the cost associated with the hospitalization were analyzed.

For event-free hospitalization, the following events were considered: death, re-infarction, cardiac pulmonary arrest (CPA), stroke, ventricular tachycardia, acute heart failure (AHF), rest chest pain and reintroduction of intravenous (IV) drugs. We performed a secondary cost analysis for patients with event-free hospitalization after the first 5 days of admission.

Results

Total of 184 patients were included, mean age 67.9 years, 70.1% male, 71.2% submitted to CABG and 20.7% to AVR (6.5% to both). During admission 23.9% of patients reintroduced IV drugs, 20.1% had chest pain, 5.4% had AHF and 2.2% had CPA. No deaths, strokes of re-infarctions were observed.

The total time of hospitalization was 3 259 patients/days, representing an occupation rate of 18.6% and a total cost of 1 898 447€ (10 318€/patient and 632 816€/year). Mean admission time was 17.6 days. Total cost for CABG and AVR patients was 1 479 613€ and 594 562€, respectively.

Total of 115 patients had an event-free hospitalization (62.5%). The total time of event-free hospitalization was 1 650 patients/days, representing an occupation rate of 9.42% and a total cost of 979 710€ (6 575€/patient and 326 570€/year). Mean event-free admission time was 14.3 days. Total cost for CABG and AVR in event-free patients was 863 155€ and 223 258€, respectively.

Conclusion

The W4S study demonstrates the impact patients waiting for surgery represent in hospital care: a very high economic and logistic burden. The majority of patients showed an event-free admission, and identifying such patients for early discharge and ambulatory management together with surgical centers should be a priority.
Implementation of sodium-glucose co-transporter 2 inhibitors in patients with heart failure through a new digital strategy (EMAIL-HF): a randomised clinical trial study design
Authors: Elmegaard M , Koeber L , Mouridsen M R , Lauridsen T K , Dridi N P , Wolsk E , Thune J J , Ersboell M K , Petersen M , Lamberts M K , Stride N O , Barasa A , Bonfils P , Tuxen C D , Schou M
Published: October 2024

Introduction

Delayed implementation of new medical discoveries remains a global healthcare challenge and is mainly due to the complexity of cross-institutional patient care. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors is the latest medical discovery in heart failure (HF) and have recently been added to clinical guidelines as they have proven to reduce the risk of adverse cardiovascular outcomes in patients with HF across the ejection fraction spectrum. Whether a new digital strategy can optimise and accelerate the implementation of SGLT2 inhibitors in patients living with HF is of great importance for public health.

Purpose

To evaluate whether a new and streamlined digital strategy can optimise and accelerate the implementation of SGLT2 inhibitors in patients with HF.

Design and methods: The trial is a multicentre, parallel group, register-based randomised clinical study, evaluating the effect and potential of a new digital strategy to implement new guideline therapies to patients living with a chronic disease, specifically SGLT2 inhibitors to patients with HF (figure 1). The setup employs data from nationwide health registers and official digital letters to inform patients about the new therapy option and invite them to have their eligibility evaluated by a HF specialist and start therapy. A total of ~10,000 patients with HF across the ejection fraction spectrum (with and without diabetes), who have not yet been started on SGLT2 inhibitors, are identified through Danish nationwide health registers, and randomised 1:1 to receive the digital letter (figure 2). The primary outcome is the proportion of patients redeeming a prescription of a SGLT2 inhibitor within six months. Secondary outcome is a composite HF endpoint consisting of all-cause death or HF hospitalisation. Other outcome measures are renal failure, stroke and myocardial infarction, safety outcomes, adherence to therapy and proportion of vulnerable patient groups initiating therapy including immigrants, elderly, frail patients, patients with lower socioeconomic level and lower educational level. A total of 4689 patients have been randomised (February 2024) and data will be presented in 2025.

Conclusions

The trial will determine the efficacy and safety of a new and streamlined digital strategy to implement SGLT2 inhibitors to patients with chronic HF. The setup has the potential to be used in a broad spectrum of patients living with chronic diseases and is expected to be highly cost-effective.Figure 1.Study hypothesisFigure 2.Study design
Phase I gene therapy clinical trial design of RP-A601 in adult patients with PKP2-arrhythmogenic cardiomyopathy (PKP2-ACM)
Authors: Coggins M , Shah M , Datto C , Narayanan B , Wishneski C , Reilly S , Parthasarathy G , Hickey L , Kasbekar S , Rossano J , Greenberg B
Published: October 2024

Background

Arrhythmogenic cardiomyopathy (ACM) is a rare, progressive, autosomal dominant disorder characterized by increased risk of ventricular arrhythmias and sudden cardiac death. Up to 45% of all ACM cases are caused by pathogenic variants in the PKP2 gene, which encodes for the desmosomal protein Plakophilin-2. This genetic cardiomyopathy is referred to as PKP2-ACM. AAVrh.74-PKP2a is a recombinant adeno-associated viral (AAV) vector containing the coding sequence of human PKP2 isoform A (PKP2a) and delivers the functional PKP2 gene to cardiomyocytes. Preclinical testing conducted in a clinically relevant mouse model of PKP2-ACM (with survival ≤50 days post disease onset) demonstrated that administration of a single AAVrh.74-PKP2a dose after disease onset extended survival through 5 months with improved right ventricular (RV) function, and decreased cardiac dilation, myocardial fibrosis, and arrhythmias. Additional studies in rodents and nonhuman primates demonstrated AAVrh.74-PKP2a safety. These preclinical findings support clinical initiation.

Purpose

We describe the design of a phase I trial to assess safety and preliminary efficacy of AAVrh.74-PKP2a (RP-A601) in high-risk adult patients with PKP2-ACM.

Methods

This study (NCT05885412) is a multi-center, open-label, dose escalation trial evaluating the safety and preliminary efficacy of a single intravenous infusion of RP-A601 in adult patients (age ≥18 yrs) with clinical and genetic PKP2-ACM diagnosis and an implanted ICD. Patients with severe right ventricular dysfunction, LV ejection fraction ≤50% (echocardiogram or cardiac MRI) and/or NYHA Class IV heart failure are excluded. Preliminary efficacy will be assessed at 12 months after RP-A601 infusion and includes evaluation of change in PKP2 myocardial tissue expression and clinical markers of arrhythmia burden.

Conclusions

PKP2-ACM is a devastating disease associated with high morbidity and mortality. This Phase I trial will evaluate the safety and preliminary efficacy of RP-A601 and was initiated based on robust preclinical efficacy and safety data.
Vaccination targeting senescence-associated transmembrane protein alleviated cardiovascular pathology in the mice
Authors: Hsiao C L , Katsuumi G , Yoshida Y , Furihata T , Joki Y , Furuuchi R , Liang J Q , Nakagami H , Minamino T
Published: October 2024

Introduction

Accumulation of senescent cells is observed in various organs including vasculature, heart and white adipose tissue with age, and known to become a substrate of pathophysiology of various cardiovascular-metabolic diseases. We have previously developed a vaccine to eliminate senescent cells, so-called "senolytic vaccine" by targeting Glycoprotein Nonmetastatic Melanoma Protein B (GPNMB) as a cellular-senescence-associated cell surface protein. We have demonstrated that GPNMB senolytic vaccine could remove senescent cells and alleviate the pathology cardiovascular-metabolic diseases. Senescence-associated adhesion molecule 1 (SAAM-1) is also known as a cell-surface membrane to increase its expression during cellular senescence in endothelial cells as well as the development of cardiovascular diseases. Here, we identified SAAM-1 as another senescence antigen and created a vaccine to eliminate senescent cells by targeting SAAM-1.

Purpose

This study was purposed to evaluate the efficacy of SAAM-1 vaccine for the treatment of cardiovascular diseases in mice models.

Methods

As a pressure overload-induced heart failure (HF) model, C57BL/6N wild type (WT) mice were underwent transverse aortic constriction (TAC) or sham opretaion at 13 weeks of age. SAAM-1 or control vaccination were given at 8 and 10 weeks of age before operation. Echocardiography examination was conducted two weeks after TAC operation, followed by tissue sampling 3 weeks after the examination. As an atherosclerosis model, ApoE KO mice were subjected to a high-fat diet (HFD) starting at 4 weeks of age. Vaccination of ApoE KO mice was administered at 8 weeks of age with SAAM-1-vaccine or control-vaccine, followed by sacrifice 4 weeks later for further analysis. ApoE-KO mice were also crossed with p16-mediated Luciferase expressing mice (p16-Luc mice) and subjected to generation of atherosclerosis model.

Results

SAAM-1 expression was significantly increased in left ventricle (LV) in TAC mice but its increase was suppressed by SAAM-1 vaccination. Interestingly, both worsening systolic function and dilatation of LV by pressure overload were significantly alleviated by SAAM-1 vaccination. Furthermore, expression level of senescent markers including p16 and p21, as well as several inflammation markers were increased in failing heart along with development of cardiac fibrosis, but SAAM-1 vaccine could significantly attenuate this pathological change. In ApoE KO mice, SAAM-1 vaccine decreased expression level of several inflammation markers in the mice, along with a decreasing p16 signal in the aorta.

Conclusions

Targeting SAAM-1 for vaccination would be a novel and promising approach to alleviating age-related cardiovascular disease.