Use of the energy waveform electrocardiogram to detect subclinical left ventricular dysfunction in patients with type 2 diabetes mellitus.

BACKGROUND: Recent guidelines propose N-terminal pro-B-type natriuretic peptide (NT-proBNP) for recognition of asymptomatic left ventricular (LV) dysfunction (Stage B Heart Failure, SBHF) in type 2 diabetes mellitus (T2DM). Wavelet Transform based signal-processing transforms electrocardiogram (ECG) waveforms into an energy distribution waveform (ew)ECG, providing frequency and energy features that machine learning can use as additional inputs to improve the identification of SBHF. Accordingly, we sought whether machine learning model based on ewECG features was superior to NT-proBNP, as well as a conventional screening tool-the Atherosclerosis Risk in Communities (ARIC) HF risk score, in SBHF screening among patients with T2DM. METHODS: Participants in two clinical trials of SBHF (defined as diastolic dysfunction [DD], reduced global longitudinal strain [GLS ≤ 18%] or LV hypertrophy [LVH]) in T2DM underwent 12-lead ECG with additional ewECG feature and echocardiography. Supervised machine learning was adopted to identify the optimal combination of ewECG extracted features for SBHF screening in 178 participants in one trial and tested in 97 participants in the other trial. The accuracy of the ewECG model in SBHF screening was compared with NT-proBNP and ARIC HF. RESULTS: SBHF was identified in 128 (72%) participants in the training dataset (median 72 years, 41% female) and 64 (66%) in the validation dataset (median 70 years, 43% female). Fifteen ewECG features showed an area under the curve (AUC) of 0.81 (95% CI 0.787-0.794) in identifying SBHF, significantly better than both NT-proBNP (AUC 0.56, 95% CI 0.44-0.68, p < 0.001) and ARIC HF (AUC 0.67, 95%CI 0.56-0.79, p = 0.002). ewECG features were also led to robust models screening for DD (AUC 0.74, 95% CI 0.73-0.74), reduced GLS (AUC 0.76, 95% CI 0.73-0.74) and LVH (AUC 0.90, 95% CI 0.88-0.89). CONCLUSIONS: Machine learning based modelling using additional ewECG extracted features are superior to NT-proBNP and ARIC HF in SBHF screening among patients with T2DM, providing an alternative HF screening strategy for asymptomatic patients and potentially act as a guidance tool to determine those who required echocardiogram to confirm diagnosis. Trial registration LEAVE-DM, ACTRN 12619001393145 and Vic-ELF, ACTRN 12617000116325.

Use of Clinical and Echocardiographic Evaluation to Assess the Risk of Heart Failure.

BACKGROUND: Clinical and echocardiographic features predict incident heart failure (HF), but the optimal strategy for combining them is unclear. OBJECTIVES: This study sought to define an effective means of using echocardiography in HF risk evaluation. METHODS: The same clinical and echocardiographic evaluation was obtained in 2 groups with HF risk factors: a training group (n = 926, followed to 7 years) and a validation group (n = 355, followed to 10 years). Clinical risk was categorized as low, intermediate, and high using 4-year ARIC (Atherosclerosis Risk In Communities) HF risk score cutpoints of 9% and 33%. A risk stratification algorithm based on clinical risk and echocardiographic markers of stage B HF (SBHF) (abnormal global longitudinal strain [GLS], diastolic dysfunction, or left ventricular hypertrophy) was developed using a classification and regression tree analysis and was validated. RESULTS: HF developed in 12% of the training group, including 9%, 18%, and 73% of low-, intermediate-, and high-risk patients. HF occurred in 8.6% of stage A HF and 19.4% of SBHF (P < 0.001), but stage A HF with clinical risk of ≥9% had similar outcome to SBHF. Abnormal GLS (HR: 2.92 [95% CI: 1.95-4.37]; P < 0.001) was the strongest independent predictor of HF. Normal GLS and diastolic function reclassified 61% of the intermediate-risk group into the low-risk group (HF incidence: 12%). In the validation group, 11% developed HF over 4.5 years; 4%, 17%, and 39% of low-, intermediate-, and high-risk groups. Similar results were obtained after exclusion of patients with known coronary artery disease. The echocardiographic parameters also provided significant incremental value to the ARIC score in predicting new HF admission (C-statistic: 0.78 [95% CI: 0.71-0.84] vs 0.83 [95% CI: 0.77-0.88]; P = 0.027). CONCLUSIONS: Clinical risk assessment is adequate to classify low and high HF risk. Echocardiographic evaluation reclassifies 61% of intermediate-risk patients.

Evaluating a new emergency department avoidance service for older people: patient and relative experiences.

BACKGROUND: High emergency department (ED) usage by older individuals for non-emergencies is a global concern. ED avoidance initiatives have proven effective in addressing this issue. To specifically cater to individuals aged 65 and above, the Southern Adelaide Local Health Network introduced an innovative ED avoidance service. This study assessed the acceptability of the service among its users. METHOD: The Complex And RestorativE (CARE) Centre is a six-bed unit staffed by a multidisciplinary geriatric team. Patients are transported directly to CARE after calling for an ambulance and being triaged by a paramedic. The evaluation took place between September 2021 and September 2022. Semi-structured interviews were conducted with patients and relatives who had accessed the service. Data analysis was performed using a six-step thematic analysis. RESULTS: Seventeen patients and 15 relatives were interviewed, who described the experience of 32 attendances to the urgent CARE centre between them. Patients accessed the service for several reasons but over half were associated with falls. There was a hesitation to call emergency services for several reasons, the primary being long wait times in ED and/or the prospect of an overnight stay in hospital. Some individuals attempted to contact their General Practitioner (GP) for the presenting problem but were unable to get a timely appointment. Most participants had previously attended a local ED and had a negative experience. All individuals reported favouring the CARE centre over the traditional ED for numerous reasons including a quieter and safer environment and specially trained geriatric staff who were less rushed than ED staff. Several participants would have appreciated a standardised follow-up process after discharge. CONCLUSION: Our findings suggest that ED admission avoidance programmes may be an acceptable alternative treatment for older people requiring urgent care, potentially benefiting both public health systems and user experience.

Facilitators and barriers to employment for persons with chronic spinal cord injury or disorder: A qualitative study framed by the person-environment-occupation model.

CONTEXT/OBJECTIVE: Prolonged unemployment is common for people living with a spinal cord injury or disorder (SCI/D) and can impact negatively on quality of life. The present study examines stakeholder perspectives and experiences with the job search process in order to identify service gaps and return-to-work solutions. DESIGN: In-depth semi-structured interviews were thematically analysed, with questions focused on factors that can help or hinder efforts to gain employment. Generated themes were then applied to the Person-Environment-Occupation (PEO) systems model of participation. SETTING: Community-based disability service provider in South Australia. PARTICIPANTS: Purposive sample of persons with SCI/D (n = 8) and rehabilitation professionals (n = 4). RESULTS: Person-centred themes were strongly endorsed by both groups and focused on incentives of, and motivation for, employment. Equally important to the job search process were individual expectations and attitudes, particularly job readiness. Environmental facilitators included employers' positive attitude, although workplace discrimination remained a concern. Occupation-based barriers, rather than opportunities, were identified - namely, difficulties in SCI/D self-management, the need for timely functional assessments, and more opportunities for education, upskilling and retraining. CONCLUSIONS: The PEO model provides a broad framework to better understand the complex return-to-work process for people with a SCI/D and, potentially, uncover tangible solutions. The suggestion is that vocational rehabilitation should go beyond skills training and include motivational support to enhance job readiness. This must be done on a case-by-case basis. There is also a need for active and covert discrimination to be addressed through employment policies. The findings will be used to develop intervention targets for a newly established vocational rehabilitation service.

Echocardiographic detection of heart valve disease in a community cohort of asymptomatic Australians > 65 years with cardiovascular risk factors.

BACKGROUND: Valvular heart disease is becoming an increasingly prevalent with population ageing. We sought to define the current prevalence of valvular heart disease in Australia. METHODS: The TasELF and VicELF studies prospectively recruited 962 asymptomatic participants ≥65 years, with at least one cardiovascular risk factor, from the Tasmanian and Victorian communities. People were excluded if they had a previous diagnosis of heart failure, or a life expectancy <1 year. All underwent baseline echocardiography. Those with moderate or severe valvular disease were identified. The current prevalence of clinically significant valve disease was applied to the Australian Bureau of Statistics population projections. RESULTS: Echocardiograms were interpretable in 943 participants (98%). Clinically significant valve disease was present in 5% of the population, and mitral regurgitation was the most common overall valvular lesion, present in 36% of the population. The projected numbers of people with clinically significant valvular disease is expected to increase significantly across all age groups by the year 2060. CONCLUSIONS: Clinically significant yet asymptomatic valvular disease was prevalent in a large community cohort of participants with at least one risk factor. The total burden of valvular heart disease is expected to increase dramatically over the coming decades.

'Put in a room and left': a qualitative study exploring the lived experiences of COVID-19 isolation and quarantine among rehabilitation inpatients.

BACKGROUND: The SARS-CoV-2 (COVID-19) pandemic has resulted in significant changes to health care delivery and the patient's experience in hospital. Changes for those who contracted COVID-19 or were close contacts included isolation and quarantine, visitor restrictions and changes to usual models of care to reduce viral transmission. Traditional models of inpatient rehabilitation utilise communal spaces (e.g. shared gyms and dining rooms) and involve a multidisciplinary team interacting with the patient daily. OBJECTIVES: To report the experience of COVID-19 related isolation and quarantine among rehabilitation inpatients and their family members who experienced a nosocomial outbreak and to make recommendations for rehabilitation units. METHODS: A qualitative phenomenological methodology using semi-structured telephone interviews. RESULTS: 19 semi-structured interviews were conducted comprising of 13 general rehabilitation inpatients and 6 family members. Five themes were established: (1) the impact of social and physical isolation; (2) boredom and limited access to therapy; (3) the impact of technology; (4) inadequate information sharing and (5) positive experiences and things done well. Several novel insights were identified including: the desire for increased social interaction from staff to compensate for a lack of visitors; the impact of physical and cognitive deficits on a patient's ability to reach basic items around their room or call for help, and the unique impact of isolation and quarantine on individuals who have a history of trauma, discrimination or mental illness. CONCLUSIONS: This study establishes key areas that should be considered by rehabilitation units globally to adjust traditional models which are not suitable in this pandemic. Strategies to mitigate the impact of isolation include providing training to increase use of technologies such as tablet devices, increased staff social engagement to reduce isolation and tailoring the environment to suit specific patient groups.KEY MESSAGESCOVID-19 related isolation and quarantine has a significant and unique impact on patients with cognitive and physical impairments such as those in inpatient rehabilitation. Patients who are required to isolate in inpatient settings expressed a desire for compensatory increased social interaction from staff and required specific assistance with basic daily tasks while isolated. The study makes key recommendations for other rehabilitation units to integrate into their approach for managing patients required to isolate or quarantine.

Association of biomarkers and risk scores with subclinical left ventricular dysfunction in patients with type 2 diabetes mellitus.

BACKGROUND: Subclinical LV dysfunction (LVD) identifies heart failure (HF) risk in type 2 diabetes mellitus (T2DM). We sought the extent to which clinical scores (ARIC-HF, WATCH-DM), natriuretic peptides (NTpBNP) and troponin (hs-TnT) were associated with subclinical LV dysfunction (LVD). These associations could inform the ability of these tests to identify which patients should undergo echocardiography. METHODS: Participants with T2DM were prospectively recruited from three community-based populations. ARIC-HF risk at 4 years and WATCH-DM scores were calculated from clinical data. NTpBNP and hs-TnT were measured using an electro-chemiluminescence assay. All underwent a comprehensive echocardiogram. We calculated the sensitivity and specificity of clinical scores and biomarkers to identify abnormal global longitudinal strain (GLS ≥ -16%)), diastolic function (E/e' ≥ 14 or e' < 8 cm/s), left atrial volume index (LAV > 34 ml/m2) and LV hypertrophy (LV mass index > 88 g/m2 (F) > 102 g/m2(M)). RESULTS: Of 804 participants (median age 69 years [inter-quartile range (IQR) 65-73], 36% female), clinical scores suggested significant HF risk (median ARIC-HF 8% [IQR 4-12]; WATCH-DM 10 points [IQR 8-12]), and the median NTpBNP was 50 pg/mL [IQR 25-101] and hs-TnT 9.6 pg/mL [IQR 6.8-13.6]. Abnormal GLS was present in 126 (17%), elevated E/e' in 114 (15%), impaired e' in 629 (78%), increased LAV in 351 (44%) and LV hypertrophy in 113 (14%). After adjustments for age, body-mass index, and renal function, each standard deviation increase in NTpBNP was associated with a GLS increase of 0.32 (p < 0.001) and hs-TnT increase by 0.26 (p < 0.001). Similar trends were observed with ARIC-HF (standardised ß = 0.22, p < 0.001) and WATCH-DM (standardised ß = 0.22, p < 0.001) in univariable analyses. However, none of the risk assessment tools provided satisfactory discrimination for abnormal GLS (AUC 63%), diastolic indices (e' AUC 54-61%) or LV mass (AUC 59-67%). At a sensitivity of 90%, there was an unacceptably low (< 50%) specificity. CONCLUSION: Although risk assessment based on clinical scores or biomarkers would be desirable to stratify HF risk in people with T2DM, they show a weak relationship with subclinical LVD.

Understanding the contribution of general medical services to acute inpatient care in Victorian public hospitals.

BACKGROUND: General medicine is an integral part of health services, yet there is little data highlighting their contribution to acute hospital care in Australia. AIMS: To utilise the Victorian Department of Health's administrative dataset for hospital admissions to evaluate the relative contribution and trends over time of general medical services to acute multiday inpatient hospital separations in the Victorian public healthcare system. METHODS: A retrospective time-series study of general medical activity compared to other major specialties using hospital-level data provided by the Department of Health: (i) extrapolation from diagnosis-related group (DRG) activity data (2011-2021) and, (ii) directly reported discharge unit-based activity (available from 2018). Acute multiday separations of all patients aged ≥18 years from all metropolitan and rural Victorian public hospitals were included. RESULTS: Using the DRG-based data, general medicine ranked as the largest care provider of all specialties studied, accounting for 12.1% of separations. Despite the largest increase at a rate of 2831 separations/year (0.336%/year of total, P < 0.001) compared to others, mean length of stay declined by 0.08 days/year (P < 0.001). These findings were significant for metropolitan and rural hospitals. The use of directly reported discharge unit-based data also ranked general medicine as the largest care provider accounting for 32.9% of total separations, with rural hospital general medical services contributing nearly 50% of all multiday separations. CONCLUSIONS: Both DRG-based data and discharge unit-based data indicate that general medicine is the largest provider of acute multiday inpatient care in Victorian hospitals. The estimate of contribution of general medicine differed between the two datasets as DRG data likely over-represents the role of other specialties possibly due to assumptions regarding specialty management of varying groups of diagnoses.

Cognitive Dysfunction in Heart Failure: Pathophysiology and Implications for Patient Management.

PURPOSE OF REVIEW: There is increasing recognition of the prevalence and impact of cognitive dysfunction (CD) in heart failure (HF) patients. This contemporary review appraises the evidence for epidemiological association, direct pathophysiological links and emerging pharmacological and non-pharmacological interventions. Furthermore, we present evidence for care models that aim to mitigate the morbidity and poor quality of life associated with these dual processes and propose future work to improve outcomes. RECENT FINDINGS: CD disproportionately affects heart failure patients, even accounting for known comorbid risk factors, and this may extend to subclinical left ventricular dysfunction. Neuroimaging studies now provide evidence of anatomical and functional differences which support previously postulated mechanisms of reduced cerebral blood flow, micro-embolism and systemic inflammation. Interventions such as multidisciplinary ambulatory HF care, education and memory training improve HF outcomes perhaps to a greater degree in those with comorbid CD. Additionally, optimisation of standard heart failure care (cardiac rehabilitation, pharmacological and device therapy) may lead to additional cognitive benefits. Epidemiological, neuroimaging and intervention studies provide evidence for the causal association between HF and CD, although evidence for Alzheimer's dementia is less certain. Specific reporting of cognitive outcomes in HF trials and evaluation of targeted interventions is required to further guide care provision.

Research activities in general medicine: a scoping survey by the Internal Medicine Society of Australia and New Zealand.

BACKGROUND: In developing an effective framework for a collaborative research network (RN) that supports members involved in research, the Internal Medicine Society of Australia and New Zealand (IMSANZ) required a better understanding of the current level of research activity and engagement by general physicians, and factors influencing such engagement. AIMS: To explore the current research landscape amongst general physicians in Australia and Aotearoa New Zealand. METHODS: A questionnaire exploring research participation, scope, research enablers and barriers was disseminated to IMSANZ members over a 3-month period. Core functions of IMSANZ-RN, research priorities, potential solutions to perceived barriers and required level of support were also evaluated. RESULTS: A total of 82 members, mostly senior medical staff (74.4%), responded to the survey (11.8% response rate). More than 70% were involved in impactful research across multiple disciplines, encompassing a wide range of research themes and topics. However, there is limited support and resources available to conduct research, with most projects being self-instigated and self-funded. There is overwhelming support to increasing the profile of research in general medicine through the establishment of IMSANZ-RN, whose principal purposes, as identified by respondents, are to foster collaboration, promote research, provide research education and training, and share information among general physicians. Quality improvement studies (56.1%) and clinical trials (41.5%) were also identified as priority research types. CONCLUSIONS: This study has profiled the constraints faced by general physicians in conducting high-quality collaborative research and provides insights into what is needed to support greater research engagement, through development of a discipline-specific clinical RN.

Screening-guided spironolactone treatment of subclinical left ventricular dysfunction for heart failure prevention in at-risk patients.

AIMS: Subclinical left ventricular dysfunction (LVD) is a prelude to symptomatic heart failure (HF). We hypothesised that screening-guided treatment with spironolactone would prevent incident HF in at-risk patients. METHODS AND RESULTS: We randomised asymptomatic, community-dwelling subjects aged ≥65 years old, with at least one non-ischaemic HF risk factor (hypertension, type 2 diabetes mellitus or obesity) to echocardiography-guided therapy or usual care. Spironolactone therapy was triggered by the detection of subclinical LVD (global longitudinal strain [GLS] ≤16%) or diastolic abnormalities (at least one of E/e' >15, E/e' >10 with left atrial enlargement [LAE] or impaired relaxation [E/A < 0.8, IR], LAE with IR), or borderline GLS (17%) with IR or borderline GLS with LAE. The primary outcome was incident HF at 24 months. Secondary outcomes were change in 6-min walk test (6MWT) and change in left ventricular function. LVD was identified in 161 (46%) of 349 participants (age 70 [68-73] years, 201 [58%] women). The trial was stopped because of a 55% rate of spironolactone discontinuation, due primarily to decline in renal function. Incident HF developed in 11 (3.5%) of 310 participants completing follow-up, with no difference between usual care and intervention (4 [2.5%] vs. 7 [4.7%], p = 0.29), decline in 6MWT distance (p = 0.28), persistent or new LVD (p = 0.58), nor change in GLS with intervention (p = 0.15). A per-protocol analysis of 131 patients with baseline LVD and a follow-up echocardiogram, showed resolution of LVD with spironolactone therapy (59% vs. 33%, p = 0.01). CONCLUSION: The study was underpowered to determine whether screening-guided spironolactone therapy reduced incident HF because spironolactone was frequently discontinued due to renal function criteria. However, LVD resolved in more patients treated with spironolactone than in untreated patients. Future trials should use less conservative renal criteria for spironolactone discontinuation.

Associations of subclinical heart failure and atrial fibrillation with mild cognitive impairment: a cross-sectional study in a subclinical heart failure screening programme.

OBJECTIVES: Effective identification and management of subclinical left ventricular (LV) dysfunction (LVD) and subclinical atrial fibrillation (AF) by screening elderly populations might be compromised by mild cognitive impairment (MCI). We sought to characterise the prevalence and profile of MCI and evaluate associations with LV and left atrial (LA) dysfunction and AF, in a trial of screening for subclinical LVD and AF. DESIGN: Cross-sectional. SETTING: Australian, community-based intervention trial. PARTICIPANTS: Adults aged ≥65 years with ≥1 LVD risk factors without ischaemic heart disease (n=337). OUTCOME MEASURES: The Montreal cognitive assessment (MoCA) was obtained. Subclinical LVD was defined as echocardiographic global longitudinal strain ≤16%, diastolic dysfunction or LV hypertrophy; abnormal LA reservoir strain (LARS) was defined as <24%. Subclinical AF was detected using a single-lead portable electrocardiographic device in those without pre-existing AF who gave consent (n=293). RESULTS: Subclinical LVD was found in 155 (46%), abnormal LARS in 9 (3.6%) and subclinical AF in 11 (3.8%). MoCA score consistent with MCI (<26) was found in 101 (30%); executive function (69%) and delayed recall (93%), were the most frequently abnormal domains. Compared with normal cognition, MCI was associated with non-adherence to AF screening (25% vs 40%, p=0.01). In multivariable logistic regression modelling, educational achievement, systolic blood pressure, body mass index and waist-to-hip ratio were independently associated with MCI. However, neither subclinical AF nor any measure of cardiac dysfunction, were associated with MCI. CONCLUSIONS: The 30% prevalence of MCI among elderly subjects with risk factors for subclinical LVD and AF has important implications for screening strategies and management. However, MCI is not associated with subclinical myocardial dysfunction nor subclinical AF. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12617000116325).

Machine Learning of ECG Waveforms to Improve Selection for Testing for Asymptomatic Left Ventricular Dysfunction.

OBJECTIVES: The purpose of this study was to identify whether machine learning from processing of continuous wave transforms (CWTs) to provide an "energy waveform" electrocardiogram (ewECG) could be integrated with echocardiographic assessment of subclinical systolic and diastolic left ventricular dysfunction (LVD). BACKGROUND: Asymptomatic LVD has management implications, but routine echocardiography is not undertaken in subjects at risk of heart failure. Signal processing of the surface ECG with the use of CWT can identify abnormal myocardial relaxation. METHODS: EwECG and echocardiography were undertaken in 398 participants at risk of heart failure (HF). Reduced global longitudinal strain (GLS ≤16%)), diastolic abnormalities (E/e' >15, left atrial enlargement with E/e' >10 or impaired relaxation) or LV hypertrophy defined LVD. EwECG feature selection and supervised machine-learning by random forest (RF) classifier was undertaken with 643 CWT-derived features and the ARIC (Atherosclerosis Risk In Communities) heart failure risk score. RESULTS: The ARIC score and 18 CWT features were selected to build a RF predictive model for LVD in a training dataset (n = 287; 60% female, median age 71 [interquartile range: 68 to 74] years). Model performance was tested in an independent group (n = 111; 49% female, median age 61 years [59 to 66 years]), demonstrating 85% sensitivity and 72% specificity (area under the receiver-operating characteristic curve [AUC]: 0.83; 95% confidence interval [CI]: 0.74 to 0.92). With ARIC score removed, sensitivity was 88% and specificity, 70% (AUC: 0.78; 95% CI: 0.70 to 0.86). RF models for reduced GLS and diastolic abnormalities including similar features had sensitivities that were unsuitable for screening. Conventional candidates for LVD screening (ARIC score, N-terminal pro-B-type natriuretic peptide, and standard automated ECG analysis) had inferior discriminative ability. Integration of ewECG in screening of people at risk of HF would reduce need for echocardiography by 45% while missing 12% of LVD cases. CONCLUSIONS: Machine learning applied to ewECG is a sensitive screening test for LVD, and its integration into screening of patients at risk for HF would reduce the number of echocardiograms by almost one-half.

Role of microvascular dysfunction in left ventricular dysfunction in type 2 diabetes mellitus.

BACKGROUND: Although microvascular disease (mVD) has been linked to poor cardiovascular outcomes in diabetes mellitus, the contribution of mVD to diabetic cardiomyopathy (DC) is unexplored. We investigated whether LV systolic and diastolic dysfunction is associated with mVD in T2DM. METHODS: We recruited 32 asymptomatic patients with T2DM (age 71 ±â€¯4 years, 31% females) from a community-based population. All underwent a comprehensive echocardiogram at baseline including assessment of global longitudinal strain (GLS) and diastolic function. Adenosine stress perfusion on cardiac magnetic resonance imaging (CMR) was performed in all patients. Coronary sinus flow (CSF) was measured offline at rest and peak stress with coronary flow reserve (CFR) calculated as the ratio of global stress and rest CSF. RESULTS: Resting CSF was reduced in 15 (47%) compared to 4 (13%) with adenosine-stress (p = 0.023). Overall, CFR was observed to be reduced in the cohort (2.38 [IQR 2.20]). Abnormal CFR was not associated with diabetes duration of ≥10 years or poor glycaemic control. CFR was not associated with abnormal GLS (OR 1.04 [95% CI 0.49, 2.20], p = 0.93). However, a modest negative correlation was observed with e' and CFR (r = -0.49, p = 0.004). CONCLUSION: This pilot study did not show correlation between subclinical systolic dysfunction and a novel MRI biomarker of microvascular disease. However, there was a weak correlation with myocardial relaxation. Confirmation of these findings in larger studies is indicated.

Development of an In Vivo Probe to Track SARS-CoV-2 Infection in Rhesus Macaques.

Infection with the novel coronavirus, SARS-CoV-2, results in pneumonia and other respiratory symptoms as well as pathologies at diverse anatomical sites. An outstanding question is whether these diverse pathologies are due to replication of the virus in these anatomical compartments and how and when the virus reaches those sites. To answer these outstanding questions and study the spatiotemporal dynamics of SARS-CoV-2 infection a method for tracking viral spread in vivo is needed. We developed a novel, fluorescently labeled, antibody-based in vivo probe system using the anti-spike monoclonal antibody CR3022 and demonstrated that it could successfully identify sites of SARS-CoV-2 infection in a rhesus macaque model of COVID-19. Our results showed that the fluorescent signal from our antibody-based probe could differentiate whole lungs of macaques infected for 9 days from those infected for 2 or 3 days. Additionally, the probe signal corroborated the frequency and density of infected cells in individual tissue blocks from infected macaques. These results provide proof of concept for the use of in vivo antibody-based probes to study SARS-CoV-2 infection dynamics in rhesus macaques.

Feasibility, Reproducibility, and Clinical Implications of the Novel Fully Automated Assessment for Global Longitudinal Strain.

BACKGROUND: Despite evidence of its usefulness, measurement of global longitudinal strain (GLS) has not been widely accepted as a clinical routine, because it requires proficiency and is time consuming. Automated assessment of GLS may be the solution for this situation. The aim of this study was to investigate the feasibility, reproducibility, and predictive value of automated strain analysis compared with semiautomated and manual assessment of GLS. METHODS: In this validation study, different methods for the assessment of GLS were applied to echocardiograms from 561 asymptomatic subjects (mean age, 71 ± 5 years) with heart failure risk factors, recruited from the community. All patients had both data on follow-up outcomes (new heart failure and cardiac death) and interpretable echocardiographic images for strain analysis. Measurement of GLS was repeated using the same apical images with three different measurement packages as follows: (1) fully automated GLS (AutoStrain), (2) semiautomated GLS (automated, corrected by a trained investigator), and (3) manual GLS (standard manual assessment by a trained investigator). RESULTS: AutoStrain measurements were technically feasible in 99.5% of patients. Calculation times for automated (0.5 ± 0.1 min/patient) and semiautomated assessment (2.7 ± 0.6 min/patient) were significantly shorter than for manual assessment (4.5 ± 1.6 min/patient; P < .001 for both). Approximately 40% of patients were thought to need manual correction after automatic calculation of GLS. Therefore, there was considerable discordance between automated and semiautomated and manual GLS. Over a median of 12 months of follow-up, cardiovascular events (new heart failure and cardiac death) occurred in 66 patients (11.8%). Automated GLS showed the potential to correctly detect normal and abnormal systolic function and predict cardiac events; the predictive value was inferior to that of semiautomated GLS. CONCLUSIONS: A novel fully automated assessment for GLS may provide a technically feasible, rapidly reproducible, and clinically applicable means of assessing left ventricular function, but a substantial number of automatic traces still need manual correction by experts. At the present stage, the semiautomated approach using this novel automated software seems to provide a better balance between feasibility and clinical relevance.

Evolution of Myocardial Dysfunction in Asymptomatic Patients at Risk of Heart Failure.

OBJECTIVES: The determinants of changes in systolic and diastolic parameters in patients age >65 years, at risk of heart failure (HF), and with and without asymptomatic type 2 diabetes mellitus (T2DM) was assessed by echocardiography. The association between metformin and myocardial function was also assessed. BACKGROUND: The increasing prevalence of T2DM will likely further fuel the epidemic of HF. Understanding the development or progression of left ventricular (LV) dysfunction may inform effective measures for HF prevention. METHODS: A total of 982 patients with at least one HF risk factor (hypertension, obesity, or T2DM) were recruited from 2 community-based populations and divided into 2 groups: T2DM (n = 431, age 71 ± 4 years) and non-T2DM (n = 551, age 71 ± 5 years). Associations of metformin therapy were evaluated in the T2DM group. All underwent a comprehensive echocardiogram, including global longitudinal strain (GLS) and diastolic function (transmitral flow [E], annular velocity [e']) at baseline and follow-up (median 19 months [interquartile range: 17 to 26 months]). Comparisons were facilitated by propensity matching. RESULTS: A reduction in GLS was observed in the T2DM group (baseline -17.8 ± 2.6% vs. follow-up -17.4 ± 2.8%; p = 0.003), but not in the non-T2DM group (-18.7 ± 2.7% vs. -18.6 ± 3.0%; p = 0.41). Estimated LV filling pressures increased in both the T2DM group (p = 0.001) and the non-T2DM group (p = 0.04). Metformin-treated patients with T2DM did not increase estimated LV filling pressure (E/e' baseline 8.9 ± 2.7 vs. follow-up 9.1 ± 2.7; p = 0.485) or change e' (7.6 ± 1.5 cm/s vs. 7.6 ± 1.8 cm/s; p = 0.88). After propensity matching, metformin was associated with a smaller change in e' (ß = 0.58 [95% CI: 0.13 to 1.03]; p = 0.013) and E/e' (ß = -0.96 [95% CI: -1.66 to -0.26]; p = 0.007) but was not associated with a change in GLS (p = 0.46). CONCLUSIONS: Over 2 years, there is a worsening of GLS and LV filling pressures in asymptomatic diabetic patients with HF risk factors. Metformin use is associated with less deterioration of LV filling pressures and myocardial relaxation but had no association with systolic function.

Impact of disease stage on the performance of strain markers in the prediction of atrial fibrillation.

BACKGROUND: Assessing atrial fibrillation (AF) risk may be useful in primary prevention (PP; people with risk factors) and secondary prevention (SP; eg. embolic stroke of unknown source). We sought whether disease stage influenced the prediction of AF by echocardiography. METHODS: We compared a PP cohort (351 community-based participants ≥65 years with ≥1 risk factor for AF) and a SP cohort (453 patients after transient ischemic attack or stroke). LV global longitudinal strain (GLS) and left atrial reservoir strain (LARS) were measured from DICOM images. AF was diagnosed by 12 lead ECG, Holter or by single lead monitor over median follow-up of 22 months (PP) and 35 months (SP). The clinical and echocardiographic characteristics of those with AF were compared to those in sinus rhythm. Nested Cox-regression models assessed for independent and incremental predictive value of LARS and GLS in both cohorts. RESULTS: AF developed in 42 PP (12%) and 60 SP (13%), and was associated with age, higher CHARGE-AF score, increased LA volume and LV mass (p < 0.05). Patients developing AF had reduced GLS (17 ± 3.5% vs. 20 ± 3%, p < 0.001) and LARS (28 ± 11% vs. 35 ± 8%, p < 0.001). However, the predictive value of both GLS (area under the ROC curve 0.83 vs 0.56, p < 0.001) and LARS (0.83 vs 0.57, p < 0.001) was greater in SP than PP. LARS was independently associated with AF in both cohorts (p < 0.05), but GLS was only independently associated in the SP cohort. CONCLUSION: AF risk assessment with LARS is suitable for different risk cohorts, but GLS is more useful in SP.