Associations between glycated haemoglobin and multi-modal imaging markers of early cardiac aging.

BACKGROUND: Glycated haemoglobin (HbA1c) is a well-established biomarker for diabetes diagnosis and management and is linked to risk of cardiovascular death. However, among adults without cardiovascular disease (CVD) and diabetes, the value of HbA1c in predicting distinct signatures of myocardial ageing has not been explored. METHODS: Subjects, from among older adults without CVD, underwent comprehensive cardiovascular and metabolic assessment. Transthoracic echocardiography measured left ventricular structure and function. Longitudinal left atrial (LA) strain comprising reservoir strain (Ɛs), conduit strain (Ɛe) and booster strain (Ɛa) and their corresponding peak strain rates (SRs, SRe, SRa) were measured using cardiac magnetic resonance (CMR). Blood sampling for biomarkers and cardiovascular examinations were performed. RESULTS: 247 subjects (mean age 71 years, 44.1% female, mean HbA1c 6.0%) were included. HbA1c was significantly associated with E/A ratio (p < 0.0001), conduit strain (Ɛe) (p < 0.0001), conduit strain rate SRe (p < 0.0001), and conduit strain rate to booster strain rate SRe:SRa ratio (p < 0.0001). Multivariate models adjusting for clinical variables such as body mass index, blood pressure, heart rate, diabetes mellitus, smoking, and associated cardiac parameters, demonstrated a persistent independent association. Each unit increase in HbA1c was associated with lower E/A ratio, lower Ɛe, higher SRe and lower SRe:SRa ratio. These associations remained significant after diabetic subjects were excluded. CONCLUSION: Distinct associations were found between HbA1c and myocardial functions of interest in the ageing heart. HbA1c may be useful biomarker for stratifying risks associated with myocardial ageing, independent of diabetes status. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02791139.

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.

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.

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.