Effects of short-term moderate intensity exercise on the serum metabolome in older adults: a pilot randomized controlled trial.

BACKGROUND: We previously reported changes in the serum metabolome associated with impaired myocardial relaxation in an asymptomatic older community cohort. In this prospective parallel-group randomized control pilot trial, we subjected community adults without cardiovascular disease to exercise intervention and evaluated the effects on serum metabolomics. METHODS: Between February 2019 to November 2019, thirty (83% females) middle-aged adults (53 ± 4 years) were randomized with sex stratification to either twelve weeks of moderate-intensity exercise training (Intervention) (n = 15) or Control (n = 15). The Intervention group underwent once-weekly aerobic and strength training sessions for 60 min each in a dedicated cardiac exercise laboratory for twelve weeks (ClinicalTrials.gov: NCT03617653). Serial measurements were taken pre- and post-intervention, including serum sampling for metabolomic analyses. RESULTS: Twenty-nine adults completed the study (Intervention n = 14; Control n = 15). Long-chain acylcarnitine C20:2-OH/C18:2-DC was reduced in the Intervention group by a magnitude of 0.714 but increased in the Control group by a magnitude of 1.742 (mean difference -1.028 age-adjusted p = 0.004). Among Controls, alanine correlated with left ventricular mass index (r = 0.529, age-adjusted p = 0.018) while aspartate correlated with Lateral e' (r = -764, age-adjusted p = 0.016). C20:3 correlated with E/e' ratio fold-change in the Intervention group (r = -0.653, age-adjusted p = 0.004). Among Controls, C20:2/C18:2 (r = 0.795, age-adjusted p = 0.005) and C20:2-OH/C18:2-DC fold-change (r = 0.742, age-adjusted p = 0.030) correlated with change in E/A ratio. CONCLUSIONS: Corresponding relationships between serum metabolites and cardiac function in response to exercise intervention provided pilot observations. Future investigations into cellular fuel oxidation or central carbon metabolism pathways that jointly impact the heart and related metabolic systems may be critical in preventive trials.

Prior studies have found changes in cellular biological processes in both cardiac aging and heart failure suggesting a common underlying mechanism. I has also been shown that exercise in healthy participants can reverse the signs of early cardiac aging. In this experimental study, we examined the effects of exercise on biological markers and cardiac function among healthy community older adults. After twelve weeks of exercise, there were changes in biological components associated with cardiac function. These findings highlight the potential of exercise as a strategy to target biological alterations in early cardiac aging and potentially prevent it.

Water Conservation Overrides Osmotic Diuresis During SGLT2 Inhibition in Patients With Heart Failure.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors are believed to improve cardiac outcomes due to their osmotic diuretic potential. OBJECTIVES: The goal of this study was to test the hypothesis that vasopressin-driven urine concentration overrides the osmotic diuretic effect of glucosuria induced by dapagliflozin treatment. METHODS: DAPA-Shuttle1 (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment) was a single-center, double-blind, randomized, placebo-controlled trial, in which patients with chronic heart failure NYHA functional classes I/II and reduced ejection fraction were randomly assigned to receive dapagliflozin 10 mg daily or placebo (1:1) for 4 weeks. The primary endpoint was change from baseline in urine osmolyte concentration. Secondary endpoints included changes in copeptin levels and solute free water clearance. RESULTS: Thirty-three randomized, sodium-glucose cotransporter 2 inhibitor-naïve participants completed the study, 29 of whom (placebo: n = 14; dapagliflozin: n = 15) provided accurate 24-hour urine collections (mean age 59 ± 14 years; left ventricular ejection fraction 31% ± 9%). Dapagliflozin treatment led to an isolated increase in urine glucose excretion by 3.3 mmol/kg/d (95% CI: 2.51-4.04; P < 0.0001) within 48 hours (early) which persisted after 4 weeks (late; 2.7 mmol/kg/d [95% CI: 1.98-3.51]; P < 0.0001). Dapagliflozin treatment increased serum copeptin early (5.5 pmol/L [95% CI: 0.45-10.5]; P < 0.05) and late (7.8 pmol/L [95% CI: 2.77-12.81]; P < 0.01), leading to proportional reductions in free water clearance (early: -9.1 mL/kg/d [95% CI: -14 to -4.12; P < 0.001]; late: -11.0 mL/kg/d [95% CI: -15.94 to -6.07; P < 0.0001]) and elevated urine concentrations (late: 134 mmol/L [95% CI: 39.28-229.12]; P < 0.01). Therefore, urine volume did not significantly increase with dapagliflozin (mean difference early: 2.8 mL/kg/d [95% CI: -1.97 to 7.48; P = 0.25]; mean difference late: 0.9 mL/kg/d [95% CI: -3.83 to 5.62]; P = 0.70). CONCLUSIONS: Physiological-adaptive water conservation eliminated the expected osmotic diuretic potential of dapagliflozin and thereby prevented a glucose-driven increase in urine volume of approximately 10 mL/kg/d · 75 kg = 750 mL/kg/d. (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment [DAPA-Shuttle1]; NCT04080518).

Current frailty knowledge, awareness, and practices among physicians following the 2022 European consensus document on Frailty in Cardiology.

Aims: Aging-related cardiovascular disease and frailty burdens are anticipated to rise with global aging. In response to directions from major cardiovascular societies, we investigated frailty knowledge, awareness, and practices among cardiologists as key stakeholders in this emerging paradigm a year after the European Frailty in Cardiology consensus document was published. Methods and results: We launched a prospective multinational web-based survey via social networks to broad cardiology communities representing multiple World Health Organization regions, including Western Pacific and Southeast Asia regions. Overall, 578 respondents [38.2% female; ages 35-49 years (55.2%) and 50-64 years (34.4%)] across subspecialties, including interventionists (43.3%), general cardiologists (30.6%), and heart failure specialists (HFSs) (10.9%), were surveyed. Nearly half had read the consensus document (38.9%). Non-interventionists had better perceived knowledge of frailty assessment instruments (fully or vaguely aware, 57.2% vs. 45%, adj. P = 0.0002), exercise programmes (well aware, 12.9% vs. 6.0%, adj. P = 0.001), and engaged more in multidisciplinary team care (frequently or occasionally, 52.6% vs. 41%, adj. P = 0.002) than interventionists. Heart failure specialists more often addressed pre-procedural frailty (frequently or occasionally, 43.5% vs. 28.2%, P = 0.004) and polypharmacy (frequently or occasionally, 85.5% vs. 71%, adj. P = 0.014) and had consistently better composite knowledge (39.3% vs. 21.6%, adj. P = 0.001) and practice responses (21% vs. 11.1%, adj. P = 0.018) than non-HFSs. Respondents with better knowledge responses also had better frailty practices (40.3% vs. 3.6%, adj. P < 0.001). Conclusion: Distinct response differences suggest that future strategies strengthening frailty principles should address practices peculiar to subspecialties, such as pre-procedural frailty strategies for interventionists and rehabilitation interventions for HFSs.

Myocardial Aging among a Population-Based Cohort Is Associated with Adverse Cardiovascular Outcomes and Sex-Specific Differences among Older Adults.

INTRODUCTION: Despite growing calls to tackle aging-related cardiovascular disease (CVD), the role of detecting early diastolic dysfunction such as those observed in aging, prior to clinical disease, is of unclear clinical benefit. METHODS: Myocardial function determined by echocardiography was examined in association with incident cardiovascular outcomes or all-cause death by Cox proportional hazards model. Sex-based differences in outcomes were included. RESULTS: A total of 956 participants (mean age 63 ± 12.9 years, n = 424 males [44%]) were categorized based on mitral peak early-to-late diastolic filling velocity (E/A) ratios: E/A <0.8 (28%), E/A 0.8-1.2 (39%), E/A (29%), E/A >2.0 (4%). Incidence rate (IR) for non-fatal cardiovascular outcomes was 2.83 per 100 person-years (95% CI: 2.24-3.56) and 0.45 per 100 person-years (95% CI: 0.26-0.80) for all-cause death. Event-free survival from non-fatal cardiovascular outcomes was significantly different among E/A categories (log-rank p = 0.0269). E/A <0.8 (HR 1.80, 95% CI: 1.031, 3.14, p = 0.039) was associated with non-fatal cardiovascular outcomes. Among men, IR for cardiovascular outcomes was 3.56 per 100 person-years (95% CI: 2.62-4.84) and 0.75 per 100 person-years (95% CI: 0.39-1.44) for all-cause death. Among women, IR for cardiovascular outcomes was 2.22 per 100 person-years (95% CI: 1.56-3.16) and 0.21 per 100 person-years (95% CI: 0.067-0.64) for all-cause death. For E/A <0.8 category, women had significantly higher risks of non-fatal cardiovascular outcomes, compared to E/A 0.8-1.2 category (HR 2.49, 95% CI: 1.18, 5.23, p = 0.017). CONCLUSION: Myocardial aging was an independent predictor of cardiovascular outcomes in community-dwelling older adults prior to clinical CVD. Impaired myocardial relaxation was prevalent in both sexes but associated with worse outcomes in women, suggestive of sex differences in age-related biology.

Adverse cardiovascular and metabolic perturbations among older women: 'fat-craving' hearts.

BACKGROUND: Despite known sex-based differences in cardiovascular aging, differences in aging biology are poorly understood. We hypothesize that circulating metabolites studied cross-sectionally with cardiac aging may be associated with cardiovascular changes that distinguish cardiac aging in women. METHODS: A population-based cohort of community men and women without cardiovascular disease from Singapore underwent detailed clinical and echocardiography examinations. Cross-sectional associations between cardiac functional characteristics and metabolomics profiles were examined. RESULTS: Five hundred sixty-seven adults (48.9% women) participated. Women were younger (72 ± 4.4 years vs 73 ± 4.3 years, p = 0.022), had lower diastolic blood pressures (71 ± 11.0 mmHg vs 76 ± 11.2 mmHg, p < 0.0001, and less likely to have diabetes mellitus (18.0% vs 27.6%, p = 0.013) and smoking (3.8% vs 34.5%, p < 0.001). Body mass indices were similar (24 ± 3.8 kg/m2 vs 24 ± 3.4 kg/m2, p = 0.29), but women had smaller waist circumferences (81 ± 10.1 cm vs 85 ± 9.2 cm, p < 0.001). Women had a significantly higher E/e' ratios (10.9 ± 3.4 vs 9.9 ± 3.3, p = 0.007) and mitral A peak (0.86 ± 0.2 m/s vs 0.79 ± 0.2 m/s, p < 0.001) than men. Among women, lower E/e' ratio was associated with higher levels of C16 (OR 1.019, 95%CI 1.002-1.036, p = 0.029), C16:1 (OR 1.06, 95%CI 1.006-1.118, p = 0.028), serine (OR 1.019, 95%CI 1.002-1.036, p = 0.025), and histidine (OR 1.045, 95%CI 1.013-1.078, p = 0.006). Lower mitral A peak was associated with higher levels of histidine (OR 1.039, 95%CI 1.009-1.070, p = 0.011), isoleucine (OR 1.013, 95%CI 1.004-1.021, p = 0.004), and C20 (OR 1.341, 95%CI 1.067-1.684, p = 0.012). CONCLUSION: Impairments in diastolic functions were more frequent among older women compared to men, despite lower prevalence of vascular risk factors and preserved cardiac structure. Cardiac aging in women correlated with metabolites involved in fatty acid oxidation and tricyclic acid cycle fuelling.

Myocarditis Following COVID-19 Vaccination: A Systematic Review (October 2020-October 2021).

INTRODUCTION: Reports of SARS-CoV-2 coronavirus (COVID-19) vaccine-related myocarditis, particularly after mRNA vaccines, have raised concerns amongst the general public. This review examined the literature regarding myocarditis post COVID-19 vaccination, drawing from vaccine safety surveillance databases and case reports. METHODS: Combinations of search terms were used in PubMed and COVID-19-specific repositories - LitCovid and the Cochrane COVID-19 Study Register - between 1 October 2020 and 31 October 2021. Manual searches of GoogleScholar and screening of article bibliographies were also performed. RESULTS: Information was obtained from five vaccine safety surveillance databases. Fifty-two (52) case reports totalling 200 cases of possible COVID-19 vaccine-related myocarditis were summarised. Vaccine surveillance databases differed in reporting formats and vaccination rates; however, gross estimates suggested low overall incidence rates of 2-5 per million mRNA vaccines. The incidence appeared to be higher in younger male populations, with onset of symptoms within a few days, usually after the second dose. Some with prior COVID-19 infections had onset after the first dose. Cases with prior unrelated myocarditis were also noted. Almost all presented with chest pain (98.0%). Troponin elevation was universally described and cardiac magnetic resonance imaging was commonly reported based on the updated Lake Louise criteria. Clinical course was mild in the majority, with response to anti-inflammatory treatment. CONCLUSION: COVID-19 vaccine-related myocarditis is an important but rare adverse event. More research is needed into its pathogenesis and reasons for its predominance in young males, while gaps in data exist in those aged <16 years, as well as those with prior COVID-19 infections and prior myocarditis.

Obesity in Older Adults and Associations with Cardiovascular Structure and Function.

INTRODUCTION: Body mass index (BMI), despite being widely used as a marker of obesity, fails to fully capture cardiovascular risks as it is an insufficient biomarker of abdominal adiposity, unlike waist circumference (WC). We aimed to characterize associations between BMI and WC with cardiovascular structure and function in older adults. METHODS: Among an observational cohort study of a community of older adults, transthoracic echocardiography determined cardiovascular structure and function, while aerobic capacity was determined by peak oxygen uptake (VO2) metrics. The cut-offs for obesity were 27.5 kg/m2 for BMI, and >90 cm for males and >80 cm for females for WC. RESULTS: Of 970 older adults without cardiovascular disease (mean age 73 ± 4 years, 432 [44%] males), 124 (12.8%) were obese by BMI definition while 347 (35.7%) were obese by WC definition. Inter-definitional agreement was fair (Cohen's κ = 0.345). Unlike the BMI definition, participants defined as obese by WC were more likely to be women (65% vs. 50%, p < 0.001), older (65 ± 11 vs. 63 ± 14 years, p = 0.007), and had lower handgrip strength (24 ± 0.6 vs. 26 ± 0.4 kg, p = 0.022). Across BMI categories, high WC was associated with more impaired myocardial relaxation (E/A), and VO2 measurements (all p < 0.05). Among those with low BMI, high WC was associated with larger left atrial (LA) volumes (p = 0.003). WC, but not BMI, was independently associated with E/A (ß = -0.114, SE -0.114 ± 0.024, p < 0.001) in regression analysis. CONCLUSION: WC identified a higher prevalence of obesity, possibly related to central adiposity. Across BMI categories, WC identified more adverse measurements in E/A, aerobic capacity, and LA structure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02791139.

Amino acid differences between diabetic older adults and non-diabetic older adults and their associations with cardiovascular function.

BACKGROUND: Ageing and insulin resistant states such as diabetes mellitus frequently coexist and increase the risk of cardiovascular disease development among older adults. Here we investigate metabolic differences in amino acid profiles between ageing and diabetes mellitus, and their associations with cardiovascular function. METHODS: In a group of community older adults we performed echocardiography, cardiac magnetic resonance imaging as well as cross sectional and longitudinal metabolomics profiling based on current and archived sera obtained fifteen years prior to examination. RESULTS: We studied a total of 515 participants (women 50%, n = 255) with a mean age 73 (SD = 4.3) years. Diabetics had higher alanine (562 vs 448, p < 0.0001), higher glutamate (107 vs 95, p = 0.016), higher proline (264 vs 231, p = 0.008) and lower arginine (107 vs 117, p = 0.043), lower citrulline (30 vs 38, p = 0.006) levels (µM) compared to non-diabetics. Over time, changes in amino acid profiles differentiated diabetic older adults from non-diabetic older adults, with greater accumulation of alanine (p = 0.002), proline (p = 0.008) and (non-significant) trend towards greater accumulation of glycine (p = 0.057) among the older diabetics compared to the older non-diabetics. However, independent of diabetes status, amino acids were associated with cardiovascular functions in ageing, [archived valine (p = 0.011), leucine (p = 0.011), archived isoleucine (p = 0.0006), archived serine (p = 0.008), archived glycine (p = 0.006) methionine (p = 0.003)] which were associated with impairments in E/A ratio. CONCLUSION: Markers of branched chain amino acids and one ­carbon metabolism pathways were associated with changes in cardiovascular function in older adults regardless of diabetes status. However, nitrogen handling pathways were specifically altered among older adults with diabetes. These findings broaden our understanding into specific amino acid pathways that may be altered between diabetic and non-diabetic older adults, and their relevance to cardiovascular function in ageing. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02791139.

Associations between cardiac function and retinal microvascular geometry among Chinese adults.

Abnormal retinal microvascular geometry has been associated with cardiac remodeling and heart failure. However, its relation to cardiac function, prior to clinical disease has not been explored. In this cross-sectional study, 50 participants (mean age 62.5 ± 11.7 years) without cardiovascular disease (CVD) were recruited from the Cardiac Ageing Study. Transthoracic echocardiography imaging was performed to measure cardiac function indices, and retinal imaging was used to measure retinal vascular caliber and retinal vascular geometric indices. Multiple linear regressions were applied to examine associations between indices of cardiac function and retinal microvasculature, adjusting for age, sex, body mass index, mean blood pressure and comorbidity (i.e. hypertension, diabetes and dyslipidemia). After adjusting for confounders, each unit decrease in peak systolic septal mitral annular velocity (Septal S') indicating poorer left function was associated with smaller retinal venular branching angle (ß: - 2.69°; 95% CI - 4.92, - 0.46). Furthermore, each unit increase in peak velocity flow in late diastole by atrial contraction (MV A Peak) indicating poorer left atrial function was associated with lower retinal venular fractal dimension (- 0.13Df; - 0.25, - 0.004). Our findings suggested a relationship between poorer cardiac function and suboptimal retinal microvascular geometry, among Chinese without CVD.

Exploring Associations Between Cardiac Structure and Retinal Vascular Geometry.

Background Retinal arteriolar narrowing and venular widening has been widely suggested to be associated with subclinical changes in cardiac structure. The novel retinal vascular geometric indices might reflect more comprehensive information on microvasculature other than vascular caliber alone. However, the association between suboptimal retinal vascular geometry and cardiac structural alteration has not been studied. Methods and Results We recruited 50 participants without cardiovascular disease from the Cardiac Aging Study conducted between 2014 and 2016. We performed transthoracic echocardiography imaging to measure cardiac structure indices such as left ventricular internal diameter end diastole index, left ventricular internal diameter end systole index, left ventricular mass index, and left atrial volume index, and retinal imaging to measure retinal vascular geometric indices including branching angle, curvature tortuosity, and fractal dimension. We applied multiple linear regressions to examine associations between indices of cardiac structure and retinal vascular geometry, adjusting for age, sex, body mass index, mean blood pressure, and comorbidity. The average age of all participants was 62.54 years old and slightly more than half were male (27; 54%). Each unit increase in a set of cardiac structure indices was associated with larger retinal arteriolar branching angle (ß and 95% CI: for left ventricular internal diameter end systole index, 26.93°; 6.00-47.86; for left ventricular internal diameter end diastole index, 17.86°; 1.61-34.11; for left ventricular mass index, 0.39°; 0.10-0.67; for left atrial volume index, 0.91°; 0.24-1.58). Conclusions Adverse retinal arteriolar geometric morphology mirrored suboptimal cardiac structural alteration.

Associations between Skeletal Muscle and Myocardium in Aging: A Syndrome of "Cardio-Sarcopenia"?

OBJECTIVES: The link between skeletal muscle and heart disease remains intriguing. It is unknown how skeletal muscle may be associated with aspects of myocardial structure and function, particularly in the presence of aging-related sarcopenia. We hypothesize that among aging adults with sarcopenia, alterations in myocardial structure and/or function may exist, resulting in a syndrome of "cardio-sarcopenia." METHODS: Participants derived from a community cohort study underwent same-day bioimpedance body composition analysis that measured skeletal muscle in sites such as the trunk, upper limb, and lower limb, and echocardiography for assessment of myocardial structure and function. Sarcopenia was diagnosed using the Asian Working Group for Sarcopenia criteria. RESULTS: We studied a total of 378 participants, of whom 88 (23.3%) had sarcopenia. Participants with sarcopenia had smaller left ventricular (LV) sizes (lower LV internal diameter end diastole (4.1 ± .7 vs 4.5 ± .6 cm; P < .0001), lower LV internal diameter end systole (2.3 ± .5 vs 2.5 ± .4 cm; P = .010), lower LV posterior wall end diastole (.7 ± .1 vs .8 ± .1 cm; P = .0036), and lower LV posterior wall end systole (1.4 ± .3 vs 1.5 ± .2 cm; P = .0031). Sarcopenic participants also had lower LV mass (106 ± 35 vs 126 ± 53; P = .0014) and lower left atrial (LA) volume (33 ± 13 vs 36 ± 13; P = .033). Adjusting for age and diabetes mellitus, skeletal muscle mass was associated with LV diameter (ß = .06; 95% confidence interval [CI] = .03-.09; P < .0001), LV mass (ß = 4.04; 95% CI = 1.78-6.29; P = .001), LA diameter (ß = .05; 95% CI = .01-.09; P = .007), and LA volume (ß = 1.26; 95% CI = .38-2.13; P = .005). A positive linear correlation was observed between LV mass and handgrip strength (r = .25; P < .0001). CONCLUSION: Among a community sample of older adults with preserved heart function, sarcopenia is associated with reductions in LV and LA sizes. Skeletal muscle mass was independently associated with specific indices of myocardial structure. J Am Geriatr Soc 67:2568-2573, 2019.

Galectin-3 as a candidate upstream biomarker for quantifying risks of myocardial ageing.

AIMS: Galectin-3 (Gal-3) is implicated in the pathogenesis of heart failure and is also influenced by ageing. This study aims to determine the extent to which Gal-3 levels estimate odds of myocardial dysfunction in ageing cohorts, 'upstream' prior to clinical disease. METHODS AND RESULTS: Four hundred seventy-five asymptomatic subjects underwent simultaneous assessments of cardiovascular structure and function, with measurements of circulating Gal-3. Myocardial dysfunction was defined as impaired myocardial relaxation (ratio of peak velocity flow in early diastole E (m/s) to peak velocity flow in late diastole by atrial contraction A (m/s) <0.84) (mean E/A ratio 0.84 in the cohort). Of 475 subjects (mean age 68 ± 12 years, 231 women), 222 (47%) had myocardial dysfunction. Subjects with myocardial dysfunction were older (mean age 73 ± 5 vs. 64 ± 14 years, P < 0.0001), and more had hypertension (59 vs. 40%, P < 0.0001), dyslipidaemia (54 vs. 39%, P = 0.001), diabetes mellitus (25 vs. 14%, P = 0.002), higher body mass index (BMI) (24 vs. 23 kg/m2 , P = 0.002), and higher heart rate (76 vs. 71 b.p.m., P = 0.0001). Participants with impaired myocardial relaxation had lower peak velocity flow in early diastole E (0.6 ± 0.1 vs. 0.8 ± 0.2 m/s, P < 0.0001), higher peak velocity flow in late diastole by atrial contraction A (0.9 ± 0.1 vs. 0.7 ± 0.2 m/s, P < 0.0001), and higher mitral valve flow deceleration time (224.7 ± 43.2 vs. 204.8 ± 33.1 m/s, P < 0.0001). Participants with impaired myocardial relaxation had higher Gal-3 levels (17.2 ± 6.2 vs. 15.5 ± 4.1, P = 0.0004) but similar B-type natriuretic peptide (37 ± 4 vs. 34 ± 29, P = 0.37) and high-sensitivity troponin I (21 ± 72 vs. 11 ± 41, P = 0.061) levels and urine microalbumin-to-creatinine ratio (4.6 ± 8.1 vs. 4.2 ± 10.8, P = 0.75) compared with those without impaired myocardial relaxation. After multivariable adjustments, Gal-3 [odds ratio (OR) 1.05, 95% confidence interval (CI) 1.00-1.10, P = 0.039], age (OR 2.60, 95% CI 1.64-4.11, P < 0.0001), BMI (OR 2.16, 95% CI 1.44-3.23, P < 0.0001), and heart rate (OR 1.04, 95% CI 1.02-1.06, P < 0.0001) were associated with impaired myocardial relaxation. Adjusted ORs (95% CI) for myocardial dysfunction were 1.0 (ref), 1.62 (0.92-2.85), 1.92 (1.08-3.41), and 2.01 (1.11-3.66) across consecutive quartiles of Gal-3 after adjustment for age, BMI, risk factors, and heart rate. CONCLUSIONS: Among asymptomatic community-dwelling elderly adults, the highest quartile of Gal-3 was associated with two-fold increased odds of myocardial dysfunction compared with the lowest quartile of Gal-3. Gal-3 may have a role as an 'upstream' biomarker in estimating odds of myocardial ageing prior to clinical disease.

N-Terminal pro C-Type Natriuretic Peptide (NTproCNP) and myocardial function in ageing.

Ageing-related alterations in cardiovascular structure and function are commonly associated with chronic inflammation. A potential blood-based biomarker indicative of a chronic inflammatory state is N-Terminal Pro C-Type Natriuretic Peptide (NTproCNP). We aim to investigate associations between NTproCNP and ageing-related impairments in cardiovascular function. Community-based participants underwent same-day assessment of cardiovascular function and circulating profiles of plasma NTproCNP. Associations between cardiovascular and biomarker profiles were studied in adjusted models including standard covariates. We studied 93 participants (mean age 73 ± 5.3 years, 36 women), of whom 55 (59%) had impaired myocardial relaxation (ratio of peak velocity flow in early diastole E (m/s) to peak velocity flow in late diastole by atrial contraction A (m/s) <0.84). Participants with impaired myocardial relaxation were also found to have lower peak early phase filling velocity (0.6 ± 0.1 vs 0.7 ± 0.1, p < 0.0001) and higher peak atrial phase filling velocity (0.9 ± 0.1 vs 0.7 ± 0.1, p < 0.0001). NTproCNP levelswere significantly lower among participants with impaired myocardial relaxation (16.4% vs 39.5% with NTproCNP ≥ 19, p = 0.012). After multivariable adjustments, NTproCNP was independently associated with impaired myocardial relaxation (OR 2.99, 95%CI 1.12-8.01, p = 0.029). Community elderly adults with myocardial ageing have lower NTproCNP levels compared to those with preserved myocardial function. Given that impaired myocardial relaxation probably represents early changes within the myocardium with ageing, NTproCNP may be useful as an 'upstream' biomarker useful for charting myocardial ageing.

Value of soluble Urokinase plasminogen activator receptor over age as a biomarker of impaired myocardial relaxation.

BACKGROUND: SuPAR is a biomarker that reflects the level of immune activation. As inflammation plays an important role in the ageing process of the cardiovascular system, we hypothesized that suPAR might be a useful predictive biomarker of the ageing heart. METHODS: We performed conventional and tissue Doppler echocardiography and measured plasma suPAR levels. RESULTS: We studied community adults (n=120, 37.5% female) (mean age: 70.3±9.3 years) without known cardiovascular disease (CVD). Participants with impaired myocardial relaxation were older (84% vs 59% were aged ≥71 years, p=0.002), with more diabetes mellitus (27% vs 11%, p=0.034). SuPAR levels were higher among participants with impaired myocardial relaxation (3.9 ng/ml vs 3.0 ng/ml, p=0.015). At the univariate level, older age (OR 3.6; 95%CI 1.6, 8.5; p=0.003), diabetes mellitus (OR 3.04; 95%CI 1.1, 8.8; p=0.04), systolic blood pressure (OR 1.03; 95%CI 1.001, 1.1; p=0.041) and suPAR levels ≥3.00ng/ml (OR 3.4; 95%CI 1.16, 7.4; p=0.002) were associated with impaired myocardial relaxation. In multivariable regression analysis, only older age (OR 2.8; 95%CI 1.1, 6.7; p=0.026) and suPAR (OR 2.7; 95%CI 1.2, 6.1; p=0.018) remained independently associated with impaired myocardial relaxation. Receiver operating characteristics (ROC) curve analysis revealed an area under the curve (AUC) value of 0.63 (95% CI 0.54, 0.71) for model that included age alone. Addition of suPAR significantly increased AUC value to 0.70 (95%CI 0.60, 0.79), which was significantly larger than the model with age alone (p=0.016). CONCLUSION: We demonstrate additional ability of suPAR, over age, to predict impaired myocardial relaxation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02791139 (Registered May 31, 2016).

Novel use of low-dose thalidomide in refractory gastrointestinal bleeding in left ventricular assist device patients.

BACKGROUND: Gastrointestinal bleeding (GIB) is a complication reported in patients post left ventricular assist device (LVAD) implantation that is associated with high mortality rates. Thalidomide is an anti-angiogenic compound that may offer a potential option for management of refractory LVAD-related GIB. METHODS: A single-center, retrospective review was conducted from January 2009 to October 2016 at a tertiary cardiology center. It included LVAD patients initiated on thalidomide for refractory GIB. RESULTS: All patients (n = 11) were started on thalidomide 50 mg nocte and there was resolution of GIB in all patients except one (90.9%) during initial thalidomide treatment.The median duration of thalidomide therapy was 98 days (interquartile range: 34-215). The dose of thalidomide was reduced for 2 patients due to adverse effects. Thalidomide therapy was discontinued in 6 patients due to cessation of GIB (n = 4) and adverse effects (n = 2). Reported adverse effects included LVAD thrombosis (n = 2), somnolence (n = 1), neuropathy (n = 1), constipation (n = 1), and transaminitis (n = 1).Recurrent GIB occurred in 4 patients (45.4%) post-discontinuation of thalidomide therapy, which led to the re-initiation of therapy. CONCLUSIONS: Thalidomide appears to be a safe and effective option for management of refractory LVAD-related GIB. Monitoring for recurrent GIB should be performed closely following cessation of thalidomide therapy.