Participant characteristics and reasons for non-consent to health information linkage for research: experiences from the ATHENA COVID-19 study.

BACKGROUND: The linkage of primary care, hospital and other health registry data is a global goal, and a consent-based approach is often used. Understanding the attitudes of why participants take part is important, yet little is known about reasons for non-participation. The ATHENA COVID-19 feasibility study investigated: 1) health outcomes of people diagnosed with COVID-19 in Queensland, Australia through primary care health data linkage using consent, and 2) created a cohort of patients willing to be re-contacted in future to participate in clinical trials. This report describes the characteristics of participants declining to participate and reasons for non-consent. METHODS: Patients diagnosed with COVID-19 from January 1st, 2020, to December 31st, 2020, were invited to consent to having their primary healthcare data extracted from their GP into a Queensland Health database and linked to other data sets for ethically approved research. Patients were also asked to consent to future recontact for participation in clinical trials. Outcome measures were proportions of patients consenting to data extraction, permission to recontact, and reason for consent decline. RESULTS: Nine hundred and ninety-five participants were approached and 842(85%) reached a consent decision. 581(69%), 615(73%) and 629(75%) consented to data extraction, recontact, or both, respectively. Mean (range) age of consenters and non-consenters were 50.6(22-77) and 46.1(22-77) years, respectively. Adjusting for age, gender and remoteness, older participants were more likely to consent than younger (aOR 1.02, 95%CI 1.01 to 1.03). The least socio-economically disadvantaged were more likely to consent than the most disadvantaged (aOR 2.20, 95% 1.33 to 3.64). There was no difference in consent proportions regarding gender or living in more remote regions. The main reasons for non-consent were 'not interested in research' (37%), 'concerns about privacy' (15%), 'not registered with a GP' (8%) and 'too busy/no time' (7%). 'No reason' was given in 20%. CONCLUSION: Younger participants and the more socio-economically deprived are more likely to non-consent to primary care data linkage. Lack of patient interest in research, time required to participate and privacy concerns, were the most common reasons cited for non-consent. Future health care data linkage studies addressing these issues may prove helpful.

2024 CSANZ Position Statement on Indications, Assessment and Monitoring of Structural and Valvular Heart Disease With Transthoracic Echocardiography in Adults.

Transthoracic echocardiography (TTE) is the most widely available and utilised imaging modality for the screening, diagnosis, and serial monitoring of all abnormalities related to cardiac structure or function. The primary objectives of this document are to provide (1) a guiding framework for treating clinicians of the acceptable indications for the initial and serial TTE assessments of the commonly encountered cardiovascular conditions in adults, and (2) the minimum required standard for TTE examinations and reporting for imaging service providers. The main areas covered within this Position Statement pertain to the TTE assessment of the left and right ventricles, valvular heart diseases, pericardial diseases, aortic diseases, infective endocarditis, cardiac masses, pulmonary hypertension, and cardiovascular diseases associated with cancer treatments or cardio-oncology. Facilitating the optimal use and performance of high quality TTEs will prevent the over or under-utilisation of this resource and unnecessary downstream testing due to suboptimal or incomplete studies.

The cost-effectiveness of coronary calcium score-guided statin therapy initiation for Australians with family histories of premature coronary artery disease.

OBJECTIVES: To compare the cost-effectiveness of coronary artery calcium (CAC) score-guided statin therapy criteria and American College of Cardiology/American Heart Association (ACC/AHA) guidelines (10-year pooled cohort equation [PCE] risk ≥ 7.5%) with selection according to Australian guidelines (5-year absolute cardiovascular disease risk [ACVDR] ≥ 10%), for people with family histories of premature coronary artery disease. STUDY DESIGN, SETTING: Markov microsimulation state transition model based on data from the Coronary Artery calcium score: Use to Guide management of Hereditary Coronary Artery Disease (CAUGHT-CAD) trial and transition probabilities derived from published statin prescribing and adherence outcomes and clinical data. PARTICIPANTS: 1083 people with family histories of premature coronary artery disease but no symptomatic cardiovascular disease. MAIN OUTCOME MEASURES: Relative cost-effectiveness over fifteen years, from the perspective of the Australian health care system, compared with usual care (Australian guidelines), assessed as incremental cost-effectiveness ratios (ICERs), with a notional willingness-to-pay threshold of $50 000 per quality-adjusted life-year (QALY) gained. RESULTS: Applying the Australian guidelines, 77 people were eligible for statin therapy (7.1%); with ACVDR 5-year risk ≥ 2% and CAC score > 0, 496 people (46%); with ACVDR 5-year risk ≥ 2% and CAC score ≥ 100, 155 people (14%); and with the ACC/AHA guidelines, 256 people (24%). The ICERs for CAC-guided selection were $33 108 (CAC ≥ 100) and $53 028 per QALY gained (CAC > 0); the ACC/AHA guidelines approach (ICER, $909 241 per QALY gained) was not cost-effective. CAC score-guided selection (CAC ≥ 100) was cost-effective for people with 5-year ACVDR of at least 5%. CONCLUSION: Expanding the number of people at low to intermediate CVD risk eligible for statin therapy should selectively target people with subclinical atherosclerosis identified by CAC screening. This approach can be more cost-effective than simply lowering treatment eligibility thresholds.

Evaluating the magnet response in deep subcutaneous implanted cardioverter defibrillator implants.

INTRODUCTION: The manufacturer of subcutaneous implantable cardioverter defibrillators (S-ICDs) acknowledges that 'deep implants' may fail to elicit a magnet response, however, does not define 'deep implant' or recommend a maximum implant depth. This study aims to systematically evaluate the effect of subcutaneous tissue depth and magnet types on evoked magnet response. METHODS: Sunshine Coast University Hospital's S-ICD cohort underwent magnet response evaluation; where bar and donut magnets were compared and the evoked magnet response was recorded in three separate zones, guided by a template. Ordinal regression (OR) models assessed the relationship between the evoked magnet response and tissue depth (TD), measured via post-implant X-Ray. The patient's ability to hear the magnet response audible tone was recorded. RESULTS: Patients (n = 39) with measurable TD (n = 30) were analyzed. The bar magnet evoked a magnet response in all zones in 53% of patients, compared with 73% of patients with the donut magnet (p = 0.18). The relationship between bar magnet response and TD showed the odds of an evoked magnet response decreased by 11% every 1 mm increase in TD (OR of 0.89, p < 0.01), whereas the donut magnet decreased by 16% per 1 mm (OR of 0.84, p < 0.01). Directly over the S-ICD was the most effective in evoking magnet response with the bar (85% of patients), and off-centre was most effective for the donut magnet (100%). BMI and Praetorian score were not significantly associated with magnet response. We found 23% of patients were unable to detect the audible tone. CONCLUSION: We observed a statistically significant association between TD and ability to evoke magnet response. The bar magnet was less reliable than the donut magnet for therapy inhibition in deep implants.

Effect of a 3-Year Lifestyle Intervention in Patients with Chronic Kidney Disease: A Randomized Clinical Trial.

BACKGROUND: Supervised lifestyle interventions have the potential to significantly improve physical activity and fitness in patients with CKD. METHODS: To assess the efficacy of a lifestyle intervention in patients with CKD to improve cardiorespiratory fitness and exercise capacity over 36 months, we conducted a randomized clinical trial, enrolling 160 patients with stage 3-4 CKD, with 81 randomized to usual care and 79 to a 3-year lifestyle intervention. The lifestyle intervention comprised care from a multidisciplinary team, including a nephrologist, nurse practitioner, exercise physiologist, dietitian, diabetes educator, psychologist, and social worker. The exercise training component consisted of an 8-week individualized and supervised gym-based exercise intervention followed by 34 months of a predominantly home-based program. Self-reported physical activity (metabolic equivalent of tasks [METs] minutes per week), cardiorespiratory fitness (peak O2 consumption [VO2peak]), exercise capacity (maximum METs and 6-minute walk distance) and neuromuscular fitness (grip strength and get-up-and-go test time) were evaluated at 12, 24, and 36 months. RESULTS: The intervention increased the percentage of patients meeting physical activity guideline targets of 500 MET min/wk from 29% at baseline to 63% at 3 years. At 12 months, both VO2peak and METs increased significantly in the lifestyle intervention group by 9.7% and 30%, respectively, without change in the usual care group. Thereafter, VO2peak declined to near baseline levels, whereas METs remained elevated in the lifestyle intervention group at 24 and 36 months. After 3 years, the intervention had increased the 6-minute walk distance and blunted declines in the get-up-and-go test time. CONCLUSIONS: A 3-year lifestyle intervention doubled the percentage of CKD patients meeting physical activity guidelines, improved exercise capacity, and ameliorated losses in neuromuscular and cardiorespiratory fitness.

Diet Quality and Protein-Bound Uraemic Toxins: Investigation of Novel Risk Factors and the Role of Microbiome in Chronic Kidney Disease.

OBJECTIVE: This study aims to explore the associations between diet quality, uraemic toxins, and gastrointestinal microbiota in the chronic kidney disease (CKD) population. METHODS: This is a baseline cross-sectional study of adults with CKD participating in a randomized controlled trial of prebiotic and probiotic supplementation. Dietary intake was measured using a seven-day diet history method, administered by a specialist dietitian. Diet quality was assessed using plant-based diet index (PDI) (overall PDI, healthy PDI, and unhealthy PDI), food group analysis, protein intake, fiber intake, and dietary protein-to-fiber ratio. Serum uraemic toxins (free and total; indoxyl sulfate and p-cresyl sulfate) were determined by ultraperformance liquid chromatography. Gastrointestinal microbiota richness, diversity, composition, and functional capacity were analyzed via metagenomic sequencing. RESULTS: Sixty-eight adults [median age: 70 (interquartile range: 58-75) years, 66% male] with an estimated glomerular filtration rate of 34 ± 11 mL/min/1.73 m2 were included, with 40 participants completing the optional fecal substudy. Dietary fiber intake was associated with lower levels of total indoxyl sulfate, whereas the healthy plant-based diet index was associated with lower levels of free p-cresyl sulfate. A higher protein-to-fiber ratio was associated with an increased relative abundance of unclassified members of order Oscillospirales. Intake of vegetables and whole grains was correlated with Subdoligranulum formicile, whereas an unclassified Prevotella species was correlated with potatoes and food items considered discretionary, including sweet drinks, sweet desserts, and animal fats. CONCLUSIONS: Diet quality may influence uraemic toxin generation and gut microbiota diversity, composition, and function in adults with CKD. Well-designed dietary intervention studies targeting the production of uraemic toxins and exploring the impact on gut microbiome are warranted in the CKD population.

Myocarditis and Cardiac Complications Associated With COVID-19 and mRNA Vaccination: A Pragmatic Narrative Review to Guide Clinical Practice.

Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus is likely to remain endemic globally despite widespread vaccination. There is increasing concern for myocardial involvement and ensuing cardiac complications due to COVID-19, however, the available evidence suggests these risks are low. Pandemic publishing has resulted in rapid manuscript availability though pre-print servers. Subsequent article retractions, a lack of standardised definitions, over-reliance on isolated troponin elevation and the heterogeneity of studied patient groups (i.e. severe vs. symptomatic vs all infections) resulted in early concern for high rates of myocarditis in patients with and recovering from COVID-19. The estimated incidence of myocarditis in COVID-19 infection is 11 cases per 100,000 infections compared with an estimated 2.7 cases per 100,000 persons following mRNA vaccination. For substantiated cases, the clinical course of myocarditis related to COVID-19 or mRNA vaccination appears mild and self-limiting, with reports of severe/fulminant myocarditis being rare. There is limited data available on the management of myocarditis in these settings. Clinical guidance for appropriate use of cardiac investigations and monitoring in COVID-19 is needed for effective risk stratification and efficient use of cardiac resources in Australia. An amalgamation of national and international position statements and guidelines is helpful for guiding clinical practice. This paper reviews the current available evidence and guidelines and provides a summary of the risks and potential use of cardiac investigations and monitoring for patients with COVID-19.

The Association Between Contrast-Enhanced Ultrasound and Near-Infrared Spectroscopy-Derived Measures of Calf Muscle Microvascular Responsiveness in Older Adults.

BACKGROUND AND AIM: Contrast-enhanced ultrasound (CEUS) measures of post-occlusion skeletal muscle microvascular responsiveness demonstrate the microvascular dysfunction associated with ageing and age-related disease. However, the accessibility of CEUS is limited by the need for intravenous administration of ultrasound contrast agents and sophisticated imaging analysis. Alternative methods are required for the broader assessment of microvascular dysfunction in research and clinical settings. Therefore, we aimed to evaluate the level of association and agreement between CEUS and near-infrared spectroscopy (NIRS)-derived measures of post-occlusion skeletal muscle microvascular responsiveness in older adults. METHODS: During supine rest, participants (n=15, 67±11 years) underwent 5 minutes of thigh cuff-occlusion (200 mmHg). Post-occlusion CEUS measures of calf muscle microvascular responsiveness were made, including time to 95% peak acoustic intensity (TTP95 AI) and the rate of rise (slope AI). Simultaneous measures, including time to 95% peak oxygenated haemoglobin (TTP95 O2Hb) and slope O2Hb, were made using continuous-wave NIRS in the same muscle region. RESULTS: There were strong correlations between TTP95 measures derived from CEUS and NIRS (r=0.834, p=<0.001) and the corresponding measures of slope (r=0.735, p=0.004). The limits of agreement demonstrated by Bland Altman plot analyses for CEUS and NIRS-derived measures of TTP95 (-9.67-1.98 s) and slope (-1.29-5.23%. s-1) were smaller than the minimum differences expected in people with microvascular dysfunction. CONCLUSIONS: The strong correlations and level of agreement in the present study support the use of NIRS as a non-invasive, portable and cost-effective method for assessing post-occlusion skeletal muscle microvascular responsiveness in older adults.

Influence of cuff-occlusion duration on contrast-enhanced ultrasound assessments of calf muscle microvascular blood flow responsiveness in older adults.

NEW FINDINGS: What is the central question of the study? Cuff-occlusion duration may influence contrast-enhanced ultrasound (CEUS) assessments of skeletal muscle microvascular blood flow responsiveness: what are the effects of 1, 3 and 5 min cuff-occlusion on the magnitude and reliability of calf muscle microvascular blood flow responsiveness in older adults? What is the main finding and its importance? Calf muscle microvascular blood flow responsiveness was enhanced following 5 min cuff-occlusion compared with 1 min. The reliability of post-occlusion CEUS measurements was also improved following 5 min occlusion. The use of a standardized 5 min occlusion period should therefore be considered in future studies and clinical practice. ABSTRACT: Contrast-enhanced ultrasound (CEUS) is increasingly used in assessments of skeletal muscle microvascular blood flow responsiveness. In response to limb cuff-occlusion, some studies have reported significant impairments in CEUS measurements of microvascular blood flow in older adults with cardiovascular or metabolic disease, whereas others have failed to detect significant between-group differences, which has brought the reliability of the technique into question. In the absence of a standardized CEUS protocol, there is variance in the duration of cuff-occlusion used, which is likely to influence post-occlusion measurements of muscle microvascular blood flow. We aimed to determine the effect of cuff-occlusion duration by comparing the magnitude and reliability of CEUS measurements of calf muscle microvascular blood flow responsiveness in older adults (n = 15, 67 ± 11 years) following 1, 3 and 5 min occlusion periods. Microvascular blood flow (= microvascular volume × microvascular velocity) within the calf muscle was measured using real-time destruction-replenishment CEUS. Measurements were made following thigh cuff-occlusion (200 mmHg) periods of 1, 3 and 5 min in a random order. Microvascular blood flow was higher following 3 min (3.71 ± 1.46 aU s-1 ) and 5 min (3.47 ± 1.48 aU s-1 ) compared with 1 min (2.42 ± 1.27 aU s-1 , P = 0.002), which corresponded with higher microvascular volumes after 3 and 5 min compared with 1 min. Reliability was good following 5 min (intraclass correlation coefficient (ICC) 0.49) compared with poor following 1 min (ICC 0.34) and 3 min (ICC 0.35). This study demonstrates that the magnitude and reliability of calf muscle microvascular responsiveness is enhanced using a 5 min cuff-occlusion protocol compared with 1 min in older adults.

Coronary artery calcium scoring in cardiovascular risk assessment of people with family histories of early onset coronary artery disease.

OBJECTIVES: To assess the predictive value of the Australian absolute cardiovascular disease risk (ACVDR) calculator and other assessment tools for identifying Australians with family histories of early onset coronary artery disease (CAD) who have coronary artery calcification. DESIGN, SETTING, PARTICIPANTS: People without known CAD were recruited at seven Australian hospitals, October 2016 - January 2019. Participants were aged 40-70 years, had a family history of early onset CAD, and a 5-year ACVDR of 2-15%. MAIN OUTCOME MEASURES: CT coronary artery calcium score greater than zero (any coronary calcification) or greater than 100 (calcification warranting lipid therapy). RESULTS: 1059 participants were recruited; 477 (45%) had non-zero coronary artery calcium scores (median 5-year ACVDR, 4.8% [IQR, 2.9-7.6%]; median coronary artery calcium score, 41.7 [IQR, 8-124]); 582 (55%) did not (median 5-year ACVDR, 3.2% [IQR, 2.0-4.6%]). Of 151 participants with calcium scores of 100 or more, 116 (77%) were deemed to be at low cardiovascular risk by Australian guidelines, while 14 of 75 participants at intermediate risk (19%) had zero calcium scores. The sensitivity of the ACVDR calculator for identifying people with non-zero calcium scores (area under receiver operator curve [AUC], 0.674) was lower than that of the pooled cohort equation (AUC, 0.711; P < 0.001). ACVDR (10-year)- and Multi-Ethnic Study of Atherosclerosis (MESA)-predicted risk categories concurred for 511 participants (48%); classifications were concordant for 925 participants (87%) when the ACVDR was supplemented by calcium scores. CONCLUSIONS: Coronary artery calcium scoring should be considered as part of the heart health check for patients at intermediate ACVDR risk and with family histories of early onset CAD. Alternative risk calculators may better select such patients for further diagnostic testing and primary prevention therapy. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN 12614001294640; 11 December 2014 (prospective).

Relationship between coronary microvascular dysfunction and left ventricular diastolic function in patients with chest pain and unobstructed coronary arteries.

BACKGROUD: Diastolic dysfunction (DD) is reported to affect up to 35% of the adult general population. The consequence of progressive DD is heart failure with preserved ejection fraction (HFpEF). Coronary microvascular dysfunction (CMD) has been suggested as one of the pathologic mechanisms leading to HFpEF. We investigated whether there was an association between coronary microvascular function and echocardiographic indices of left ventricular diastolic function at rest in patients with chest pain and unobstructed coronary arteries (CPUCA). METHODS: This retrospective observational study recruited patients referred to cardiology clinics assessment of chest pain who subsequently underwent assessment via CT coronary angiogram (CTA). Coronary microvascular dysfunction was determined by myocardial blood flow reserve (MBFR; <2.0) using myocardial contrast echocardiography. Echocardiographic indices of diastolic function (septal mitral annular e'; septal mitral annular E/e', E/A ratio) were measured from baseline transthoracic echocardiogram. RESULTS: 149 patients (52% men) with a mean age 59.7(9.5) years were recruited. Mean (standard deviation) MBFR was 2.2 (0.51). 37% (55/149) had MBFR < 2.0. Median [interquartile range] septal mitral annular e' velocity and septal mitral annular E/e' were 7.6 cm/s [6.2, 8.9] and 9.5 [7.5, 10.8], respectively. Univariate regression analysis showed only age was a significant predictor of increasing septal mitral annular E/e' (ß = +0.20 95% CI 0.13, +0.28, P < .001) but not MBFR. Multivariable analysis also showed no association between these septal mitral annular E/e' and MBFR after adjustment for cardiovascular risk factors. CONCLUSION: There was no relationship found between echocardiographic indices of left ventricular diastolic function and coronary microvascular function at rest.

CSANZ Imaging Council Position Statement on Echocardiography Services During the COVID-19 Pandemic.

This Cardiac Society of Australia and New Zealand (CSANZ) Imaging Council Position Statement aims to guide local, regional and national clinical practice, and facilitate resource and echocardiographic service planning appropriately during the current COVID-19 global pandemic. General considerations include workforce arrangements and contingency plans, patient risk assessment for COVID-19 and level of care (personal protective equipment) for staff. Both outpatient and inpatient settings are addressed, including specific considerations in the in-patient setting including scanning protocols, screening modalities and indications for echocardiograms in the context of COVID-19 infection.

Echocardiographic Strain in Clinical Practice.

The accurate evaluation of left ventricular (LV) function has been central to monitoring of therapy, institution of specific therapeutic interventions and as a prognostic marker for risk stratification in a variety of cardiovascular conditions. However, LV ejection fraction, the most commonly used measure of LV systolic function, is a 'coarse' measure of global LV function, with several limitations. Strain analysis, a measure of myocardial deformation, has come to the forefront more recently as a more sensitive measure of myocardial function than LV ejection fraction. Its utility in detection of early subclinical LV dysfunction, defining regional variation in specific cardiomyopathies, utility to monitor improvement with therapy and as a prognostic marker in a variety of cardiac conditions has led to its increasing use in clinical practice. This review will briefly summarise specific methodological aspects, use in diagnosis and prognostic utility of strain analysis in various cardiovascular conditions.

The Clinical Utility and Enduring Versatility of Stress Echocardiography.

Stress echocardiography is an established cardiac imaging modality for the detection and quantification of severity of coronary artery disease. In recent years, there has also been an increasing use of stress echocardiography in the assessment of non-ischaemic cardiac disease given its ability to assess functional capacity and haemodynamic changes with exercise which can help guide therapy and inform prognosis. The emerging use of strain, myocardial contrast and three-dimensional (3D) echocardiography further assists in improving diagnostic accuracy particularly in patients with coronary artery disease. This paper summarises the protocols, indications and clinical applications of stress echocardiography in both ischaemic and non-ischaemic cardiac disease.

Rationale and design of a trial to personalize risk assessment in familial coronary artery disease.

BACKGROUND: The lifetime risk of coronary artery disease (CAD) is doubled in people with a family history of premature disease, yet this risk is not captured in most 5- or 10-year risk assessment algorithms. Coronary artery calcium scoring (CCS) is a marker of subclinical CAD risk, which has been shown in observational studies to provide prognostic information that is incremental to clinical assessment; is relatively inexpensive; and is performed with a small radiation dose. However, the use of CCS in guiding prevention is not strongly supported by guidelines. Showing definitive evidence of the efficacy and cost-effectiveness of CCS is therefore of importance. STUDY DESIGN: The proposed randomized controlled trial of the use of CCS will be targeted to 40- to 70-year-old first-degree relatives of patients with CAD onset <60 years old or second-degree relatives of patients with onset <50 years old. Control patients will undergo standard risk scoring and be blinded to CCS results. In the intervention group, primary prevention in patients undergoing CCS will be informed by this score. At 3 years, effectiveness will be assessed on change in plaque volume at computed tomography coronary angiography, the extent of which has been strongly linked to outcome. SUMMARY: The CAUGHT-CAD trial will provide evidence to inform the guidelines regarding the place of CCS in decision making regarding primary prevention of patients with a family history of premature disease.

Effects of post-discharge management on rates of early re-admission and death after hospitalisation for heart failure.

OBJECTIVES: To investigate whether enrolment of patients in management programs after hospitalisation for heart failure (HF) reduces the likelihood of post-hospital adverse outcomes. DESIGN: Cohort study in which associations between adverse outcomes at 30 and 90 days for people hospitalised for HF and baseline clinical, socio-demographic and blood pathology factors, and with post-discharge management strategies, were assessed. Setting, participants: 906 patients with HF were prospectively enrolled in five Australian states at cardiology departments with expertise in treating people with HF. MAIN OUTCOME MEASURES: All-cause re-admissions and deaths at 30 and 90 days after discharge from the index admission. RESULTS: 58% of patients were men; the mean age was 72.5 years (SD, 13.9 years). By hospital, 30-day re-admission rates ranged from 17% to 33%, and 90-day rates from 40% to 55%; 30-day mortality rates were 0-13%, 90-day rates 4-24%. Factors associated with increased odds of re-admission or death at 30 or 90 days included living alone, cognitive impairment, depression, NYHA classification, left atrial volume index, and Charlson index score. Nurse-led disease management programs and reviews within 7 days were associated with reduced odds of re-admission (but not of death) at 30 and 90 days; exercise programs were associated with reduced odds at 90 days. Significant between-hospital differences in re-admission rates were reduced after adjustment for post-discharge management programs, and abolished by further adjustment for echocardiography findings. Between-hospital differences in mortality were largely explained by differences in echocardiographic findings. CONCLUSIONS: Differences in early re-admission rates after hospitalisation for HF are primarily explained by differences in post-discharge management.

Carvedilol and Cardiac Biomarkers in Dialysis Patients: Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND/AIMS: Cardiac biomarkers are associated with cardiac abnormalities and adverse outcomes in dialysis patients. Our aim was to report the effect of the beta-blocker carvedilol on cardiac biomarkers in adult dialysis patients. METHODS: The Beta-Blocker to Lower Cardiovascular Dialysis Events Feasibility Study was a randomized controlled trial comparing carvedilol to placebo. Serum and plasma were collected before the run-in, then 6 and 12 months post-randomization to measure B-type Natriuretic Peptide (BNP), N-terminal BNP (NT-ProBNP), high-sensitivity cardiac troponins I (hs-TnI) and T (hs-TnT), and galectin-3. Left ventricular global longitudinal strain (GLS) was measured by echocardiography at baseline. RESULTS: Seventy-two participants were recruited of whom 49 completed the run-in and were randomized to carvedilol (n=26) or placebo (n=23). Baseline echocardiography demonstrated median (inter-quartile range) GLS of -14.27% (-16.63 to -11.93). NTproBNP and hs-TnT correlated with GLS (Spearman's rho=0.34 [p=0.018] and rho=0.28 [p=0.049], respectively). Median change scores from baseline to 12 months did not differ significantly between participants with complete biomarker data randomized to carvedilol (n=15) or placebo (n=16) for any biomarkers. CONCLUSIONS: NT-proBNP and hs-TnT were associated with GLS. However, changes in levels of the biomarkers from baseline to 12 months were not different between groups randomized to carvedilol and placebo.

Progression of arterial stiffness is associated with changes in bone mineral markers in advanced CKD.

BACKGROUND: Arterial stiffness is an independent predictor of all-cause and cardiovascular mortality in patients with chronic kidney disease (CKD). There are limited prospective data however on progression of arterial stiffness in CKD, including evaluating associations with bone mineral markers such as fibroblast growth factor 23 (FGF23) and soluble α-klotho (sKl). METHODS: In this prospective, single-center, observational study, arterial stiffness [measured by pulse wave velocity (PWV)] and hormones influencing mineral homeostasis, including serum FGF23 and sKl, were compared between non-dialysis CKD stages 4/5 and healthy controls at baseline and 12 months (12 m). Abdominal aortic calcification (AAC) was quantitated using lateral lumbar radiography at baseline. RESULTS: Forty patients with CKD [mean estimated glomerular filtration rate (eGFR) 19.5 ± 6.7 mL/min/1.73m2] and 42 controls (mean eGFR 88.6 ± 12.9 mL/min/1.73m2) completed follow-up. There were no differences in age, gender and body mass index between groups. A significant increase in FGF23 [240.6 (141.9-1129.8) to 396.8 (160.3-997.7) pg/mL, p = 0.001] was observed in the CKD group but serum phosphate, corrected calcium, parathyroid hormone and sKl did not change significantly over 12 m. At baseline, CKD subjects had higher AAC prevalence [83.8% versus (vs.) 43.6%, p = 0.002] and higher aortic PWV [9.7(7.6-11.7) vs. 8.1 (7.2-9.7) m/s, p = 0.047] compared to controls. At 12 m, aortic PWV increased by 1.3 m/s (95% confidence interval, 0.56 to 2.08, p < 0.001) in the CKD cohort, with 30% of subjects showing progression from normal aortic elasticity to stiffening (PWV > 10 m/s). Serum FGF23 was associated with AAC, abnormal PWV and progression of PWV at 12 m. CONCLUSIONS: Arterial stiffness and serum FGF23, both of which are associated with increased cardiovascular risk, increased over one year in individuals with CKD. Additionally, a significant association was found between serum FGF23 and arterial calcification and stiffness. Larger clinical studies and further experimental work are warranted to delineate the temporal relationship as well as the pathological mechanisms linking FGF23 and vascular disease.