BACKGROUND:We aimed to evaluate the risks and outcomes of coronary artery bypass grafting in patients aged ≥80 years in Australia. METHOD:We conducted a retrospective cohort study of 96,849 patients who underwent isolated coronary artery bypass surgery between 1 January 2001 and 31 December 2022, using data from the Australian and New Zealand Society of Cardiac and Thoracic Surgeons cardiac surgery database. Patients were stratified into octogenarians and non-octogenarians. Primary outcomes included operative mortality (30-day or in-hospital death) and long-term survival. Kaplan-Meier estimates were used to analyse survival, logistic regression to identify predictors of early mortality, and Cox proportional hazards to identify predictors of late mortality. Survival in the octogenarian cohort was compared with an age- and sex-matched Australian population. RESULTS:Operative mortality was 2.8% in octogenarians vs 1.0% in non-octogenarians. The median follow-up was 3.4 years, with Kaplan-Meier estimated survival rates of 93%, 72%, 37% and 14% at 1, 5, 10, and 15 years. Median survival was 8.0 years in octogenarians, compared to 6.7 years in an age- and sex-matched general Australian population. The standardised mortality ratio was 0.78 (95% confidence interval 0.75-0.82; p<0.001). CONCLUSIONS:Although octogenarians undergoing coronary artery bypass have a higher operative risk than younger patients, mortality rates are lower than previously reported. Surgery in this population may be associated with favourable long-term survival compared to the general population. These findings support careful patient selection and shared decision-making when considering surgical revascularisation in the elderly.

AIM:There are limited data on the prevalence of calcific aortic valve disease (CAVD) in Māori and known inequities in outcomes after aortic valve intervention. Our study aimed to investigate the prevalence of CAVD in Māori. METHODS:Data from initial clinically indicated echocardiograms performed between 2010 to 2018 in patients aged ≥18 years were linked to nationally collected outcome data. Ethnicity was defined using protocols from the Ministry of Health. RESULTS:Of the 23,635 patients, 1,312 (5.6%) identified as Māori, and 22,323 (94.4%) as European. Prevalence of aortic stenosis was 5.3% in Māori and 9.9% in Europeans. Age-specific prevalence did not differ between the two groups. Māori with CAVD were more than twice as likely to have advanced cardiac impairment (right ventricular dysfunction) than Europeans (10.1% vs 4.6, p<0.001). CONCLUSIONS:Age-specific CAVD rates did not differ between Māori and Europeans, though Māori had a higher proportion of advanced cardiac impairment, which is likely unrelated to CAVD. Differences in population structure likely explain the difference in overall prevalence of CAVD. The improving life expectancy in Māori may lead to increasing incidence of CAVD, thus strategies to improve detection and medical management of CAVD should begin as soon as possible.

Patients with ischaemic heart disease (IHD) require frequent monitoring, as the transition from stable disease to acute life-threatening events remains largely unpredictable. MicroRNAs (miRNAs), small non-coding RNAs involved in physiological and pathological processes, are released into circulation and remain stable. In this study, we aimed to determine if the serial measurement of cardiovascular-enriched circulating miRNAs could reflect changes in cardiac function in patients with IHD. Fifty-three new IHD patients participated in a five-year study with regular echocardiography, blood tests and follow-ups at 12-month intervals, with 25 followed up at five years. Serial echocardiography revealed a pattern towards worsening diastolic function over the follow-up period. RT-PCR analysis was conducted on four cardiovascular-enriched circulating miRNAs: miR-1, miR-126, miR-132 and miR-34a. Among these, only miR-1 and miR-126 showed statistically significant down-regulation starting from 24 months onwards. Linear mixed models, adjusted for body mass index and HbA1c changes, indicated significant associations between fold changes in miR-1 and miR-34a with cardiac function changes. Results from this first-ever five-year follow-up study have identified a possible link between cardiovascular-enriched miRNAs, miR-1 and -34a and cardiac function in patients with IHD, providing a foundation for prognostic tests for IHD and laying the foundation for further studies in larger populations. It is noteworthy that a significant dropout of participants may have impacted the statistical power in our study.

The objective of this study was to characterize the 24-h blood pressure response following an acute hot-water immersion exposure, specifically examining the effect of immersion duration and water temperature, in people with hypertension. Sixteen participants (11 females; 62 ± 7 y; 31.7 ± 7.5 kg.m-2) with hypertension (taking at least one anti-hypertensive medication) completed four randomized sessions: 1) 20-min and 2) 40-min hot-water immersion (40°C), 3) 40-min thermoneutral immersion (36.5°C), and 4) control (seated, no immersion). Blood pressure, heart rate, perceptual and affective responses were recorded throughout exposure. Immediately after exposure, participants were fitted with an ambulatory blood pressure monitor for the following 24 h. Twenty-four-hour SBP was 7 mm Hg lower (95% CI: -11, -2; p = 0.001) after the 40-min hot-water immersion and 6 mm Hg lower after both the 20-min hot-water immersion (-10, -1; p = 0.006) and 40-min thermoneutral immersion (-9, -3; p = 0.002) compared to control; these effects were similar across nighttime (i.e. 10 pm-6 am) and daytime periods. Twenty-four-hour DBP was not statistically different across any exposure (p = 0.093). The percentage of 24 h in target range for SBP (110-130 mm Hg) more than doubled (39% vs. 18%) following the 40-min hot-water immersion, compared to control. Clinically meaningful decreases in systolic blood pressure were evident with hot-water immersion in people with hypertension; these effects were present irrespective of immersion duration (i.e. 20 min vs. 40 min) or water temperature (36.5°C vs 40°C).

We recently found that plasminogen receptors regulate the plasma membrane binding and uptake of Lp(a) via macropinocytosis. In this study, we sought to further define lipoprotein(a) [Lp(a)] macropinocytosis, discovering an unexpected role for antidepressants and serotonin in the regulation of this process. We found that the tricyclic antidepressant imipramine enhanced Lp(a) uptake, in contradiction of its published role as a macropinocytosis inhibitor. Extending these experiments to the commonly used serotonin uptake inhibitors (SSRIs) citalopram, sertraline, fluoxetine, and paroxetine, we found that citalopram and paroxetine stimulated Lp(a) uptake. Imipramine and citalopram enhanced cell surface binding of Lp(a) to increase uptake by macropinocytosis. Consistent with imipramine and citalopram boosting extracellular serotonin levels, serotonin itself also enhanced Lp(a) surface binding and uptake. In contrast to Lp(a), imipramine and citalopram had no effect on low-density lipoprotein (LDL) uptake. Imipramine and serotonin increased expression of the plasminogen receptor with a C-terminal lysine (PlgRKT), a receptor known to enhance cell surface binding of Lp(a), likely accounting for their effects on Lp(a) uptake. Finally, imipramine and citalopram increased Lp(a) delivery into Rab11 recycling endosomes but not degradative pathways in the cell. These findings indicate SSRIs such as citalopram and paroxetine may have utility as a potential Lp(a)-lowering therapeutic in people suffering from depression who often have elevated Lp(a) levels and an increased risk of cardiovascular disease.

AIM:The aim of this study was to assess the effect of pre-operative cardiorespiratory fitness (peak VO2) on physical and subjective recovery from total hip or knee arthroplasty. A secondary aim was to assess the relationship between daily step count or estimated peak VO2 via the Duke Activity Status Index (DASI) questionnaire, on post-operative recovery. METHODS:In this secondary analysis of a prior randomised controlled trial, 51 patients (69 [8] y; 25 female; peak VO2: 20.1 [7.8] mL/min/kg) scheduled for total hip (n=23) or knee (n=28) arthroplasty underwent pre-operative assessment (cardiopulmonary exercise testing, physical function tests [30-second sit to stand, timed up and go, knee range of motion]), accelerometry and subjective questionnaire (DASI). Post-operative assessments included length of hospital stay, the Surgical Recovery Scale (SRS) and repeated functional assessments. RESULTS:A low pre-operative peak VO2 (i.e., <15mL/min/kg) was associated with five fewer sit-to-stand reps (95% CI [confidence interval]: 3 to 7; p=0.002), 3,500 fewer daily steps (95% CI: 1,053 to 5,867; p=0.006) and poorer subjective surgical recovery at 7-days (-12 arbitrary units [AU], 95% CI: -3 to -22, p=0.014) and 6-weeks post-operative (-13 AU, 95% CI: -5 to -21; p=0.003). Estimated pre-operative peak VO2 using the DASI questionnaire was moderately correlated with post-operative daily step count (r=0.51, p <0.001); post-operative daily step count increased by 500 steps for every 1mL/min/kg increase in estimated peak VO2. CONCLUSION:Pre-operative peak VO2 was associated with physical and subjective recovery following total hip or knee arthroplasty. Daily step count and estimated peak VO2 via the DASI questionnaire had similar moderate associations with post-operative functional outcomes as directly measured pre-operative peak VO2 and may be acceptable alternatives to predict recovery following hip or knee arthroplasty.

AIMS:Cohort studies have demonstrated associations between calcific aortic valve disease (CAVD) and Lp(a). As Lp(a) is almost entirely genetically determined, in this study, we aim to determine whether Lp(a), when predicted from genetic data, is associated with CAVD and major adverse cardiovascular events (MACEs). METHODS AND RESULTS:Patients undergoing coronary angiography between January 2012 and May 2013 were invited to participate in the study. Of 752 analysable participants, 446 had their Lp(a) measured and 703 had a calculable LPA genetic risk score (GRS). The primary outcomes were the presence of CAVD at baseline and MACE over a 7-year follow-up. The GRS explained 45% of variation in Lp(a). After adjustment for cardiac risk factors and coronary artery disease (CAD), the odds of CAVD increased with increasing Lp(a) [odds ratio (OR) 1.039 per 10-unit increase, 95% confidence interval (CI) 1.022-1.057, P < 0.001] and GRS (OR 1.054 per 10-unit increase, 95% CI 1.024-1.086; P < 0.001). Lipoprotein(a) and the GRS as continuous variables were not associated with subsequent MACEs. A dichotomized GRS (>54) was associated with MACE, but this relationship became non-significant when CAD classification was added into the model (OR 1.333, 95% CI 0.927-1.912; P = 0.12). CONCLUSION:An LPA GRS can explain 45% of variation in Lp(a) levels, and both Lp(a) and the GRS are associated with CAVD. An elevated GRS is associated with future cardiac events in a secondary risk setting, but, if the CAD status is known, it does not provide additional prognostic information.

Abstract Aims Previous studies have demonstrated relatively slow rates of progression of early calcific aortic valve disease (CAVD), which encompasses aortic sclerosis (ASc) and mild aortic stenosis (AS). The potential evolution to clinically significant AS is unclear, and we therefore examined the long-term outcomes of patients with ASc and mild AS detected at the time of clinically indicated echocardiography. Methods and results Data from initial clinically indicated echocardiograms performed between 2010 and 2018 in patients aged ≥18 years were extracted and linked to nationally collected outcome data. Those with impaired right or left systolic ventricular function or other significant left-sided valve disease were excluded. A time to first event analysis was performed with a composite primary outcome of cardiovascular death and aortic valve intervention (AVI). Of the 13 313 patients, 8973 had no CAVD, 3436 had ASc, and 455 had mild AS. The remainder had moderate or worse stenosis. Over a median follow-up period of 4.2 (interquartile range 1.8–6.7) years (and after adjustment for age and sex), those with ASc were at greater risk of the primary outcome [hazard ratio (HR) 2.9, 95% confidence interval (CI) 2.1–4.0] and need for AVI (HR 26.8, 95% CI 9.1–79.1) compared with those with no CAVD. Clinical event rates accelerated after ∼5 years in those with mild AS. Conclusion Patients with ASc are >25 times more likely to require AVI than those with no CAVD, and follow-up echocardiography should be considered within 3–4 years in those with mild AS.

AbstractBackgroundA staging system for aortic stenosis (AS) based upon the extent of cardiac damage has been proposed to better stratify risk and evaluate the benefit of aortic valve intervention (AVI), especially in those with moderate AS. We sought to evaluate the prognostic value of this staging system.MethodsData from initial clinically indicated echocardiograms performed between 2010 and 2018 in patients >18 years of age were extracted and linked to national outcome data. The combined primary outcome was mortality or hospitalization with heart failure.ResultsAmongst 24,699 patients, 513 and 920 had moderate and mild AS, respectively. In moderate AS, Stage 0 cardiac damage was present in 9.4%, Stage 1 in 53.7%, Stage 2 in 31.1%, Stage 3 in 3.2%, and Stage 4 in 2.6%. In mild AS, rates were 11.5%, 57.8%, 25.0%, 2.6%, and 3.0% for each consecutive stage. Increasing stage was associated with increased risk of the primary outcome in both moderate (HR 1.62/stage) and mild AS (HR 1.93/stage). After censoring at the time of AVI, increasing stage was also associated with mortality in moderate (HR 1.97/stage) and mild AS (HR 2.06/stage).ConclusionStage of cardiac damage predicts prognosis in both moderate and mild AS to a similar extent. Outcomes may therefore not be fully related to the haemodynamic consequences of valve disease, and hence may not be entirely reversible after valve intervention. Revised management algorithms focusing on earlier intervention and novel treatment strategies targeting cardiac damage are needed to improve clinical outcomes in patients with AS.

Background: Patients with ischemic heart disease (IHD) require frequent monitoring, as the transition from stable disease to acute life-threatening events remains largely unpredictable. Currently available tests are either not sensitive enough to detect early changes or not easily incorporated into routine clinical practice. MicroRNAs (miRNAs), small non-coding RNAs involved in both physiological and pathological processes, are released into circulation and remain stable. Research Question: In this study, we aimed to determine if the serial measurement of cardiovascular-enriched circulating miRNAs could reflect changes in cardiac function in patients with IHD. Methods: Fifty-four new IHD patients joined a 5-year study, providing informed consent for regular echocardiography, blood tests and follow-ups at 12-month intervals. Plasma RNA was extracted and RT-PCR analysis used to assess expression of cardiovascular-enriched miR-1, miR-126, miR-132, and miR-34a. Results: Serial echocardiography analysis showed the development of diastolic dysfunction in the participants starting from 48 months (E/e’-10.7±4.3 vs 9.7±3.6 at baseline, P<0.04). RT-PCR analysis revealed significant downregulation of miR-1 and miR-126 starting from 24 months of follow-up (P<0.03 vs. baseline). Associations between each miRNA and each cardiac function measure were examined using linear mixed models without and with adjustment for changes in BMI and HbA1c during the same period. None of the lagged models found statistically significant associations (all p ≥ 0.126). From the concurrent models, two miRNA were associated with cardiac function: miR-1 and MV E Vel in the unadjusted (p = 0.045) and adjusted models (slope = -0.004, 95% CI -0.007 to -0.000, p = 0.026) models and miR-34a and FS(%) in the adjusted model only (slope = -0.151, 95% CI -0.301 to -0.001, p = 0.048). Conclusion: Results from this first-ever five-year follow-up study have identified a link between cardiovascular enriched miRNAs, miR-1 and -34a and cardiac function in patients with IHD, providing a knowledge platform for prognostic tests for IHD and laying the foundation for further studies in larger population size.

Abstract Title: Cardiac damage predicts the outcome of patients with calcific aortic valve disease in both mild and moderate aortic stenosis Background Although the burden of calcific aortic valve disease (CAVD) is increasing, there is no current universal consensus for prognostic prediction. A staging system based on cardiac damage has been proposed to better stratify risk and evaluate the benefit of aortic valve intervention (AVI). Purpose We sought to evaluate this staging system’s prognostic value in mild and moderate aortic stenosis (AS). Methods Data from clinically indicated echocardiograms performed between 2010 and 2018 in patients aged over 18 years were extracted and linked to national outcome data. A time to first event analysis was performed with a primary outcome of mortality or heart failure hospitalization. Stages were categorized as described in previous literature: no extravalvular damage (stage 0); left ventricular damage (stage 1); left atrial damage (stage 2); elevated right ventricular pressures (stage 3); or right ventricular damage (stage 4). Results Amongst 24,699 patients in the study cohort, 513 had moderate AS and 920 had mild AS. Associated cardiac damage in those with moderate AS was graded as follows: Stage 0 - 9.4%; Stage 1 - 53.7%; Stage 2 - 31.1%; Stage 3 - 3.2%; Stage 4 - 2.6%. Increasing severity of CAVD correlated closely with increased risk of the primary outcome in both moderate (HR 1.62 per stage; 95% CI 1.36 – 1.92) and mild AS (HR 1.93 per stage; 95% CI 1.69 – 2.21), whilst increasing stage of cardiac damage was associated with mortality when censoring at the time of AVI in both moderate (HR 1.97 per stage; 95% CI 1.66 – 2.34) and mild AS (HR 2.06 per stage; 95% CI 1.81 – 2.35). Conclusion Cardiac dysfunction predicts prognosis to a similar extent in both mild and moderate AS. These data suggest that adverse outcomes may not be fully attributable to the haemodynamic consequences of valve disease, and therefore may not be reversed by valve intervention. Strategies to treat cardiac dysfunction in parallel with management of the anatomical valve pathology may be required.Mortality in mild AS by CAVD stageMortality in moderate AS by CAVD stage

ABSTRACT Objective We investigated whether childhood social isolation was associated with retinal neural layer changes in adulthood, and whether this association was independent of other childhood or adulthood risk factors, including adult social isolation. Methods Participants were members of the Dunedin Multidisciplinary Health and Development Study, a longitudinal population-based birth cohort from Aotearoa New Zealand ( n = 1037), born 1972 to 1973 and followed until age 45 years, with 94% of the living cohort still participating. Social isolation was recorded prospectively at ages 5, 7, 9, and 11 years, from teacher and parent report. Retinal nerve fiber layer (RNFL) and ganglion cell–inner plexiform layer thicknesses were measured via optical coherence tomography at age 45 years. Results Childhood social isolation was associated with thinner average RNFL ( B = −0.739, p = .02), nasal RNFL ( B = −1.118, p = .005), and inferior RNFL ( B = −1.524, p = .007), although only nasal RNFL remained significant after adjustment. These associations were not fully explained by other psychosocial or physical health risk factors in childhood or adulthood, nor were they mediated by adult loneliness or social support. Conclusions Childhood social isolation was an independent predictor of RNFL thickness in middle age. Highlighting prospective links between childhood psychosocial adversity and retinal neuronal measures will help to inform future research into the utility of retinal neuronal thickness as a biomarker for neurodegeneration.

BACKGROUND: High levels of Lp(a) (lipoprotein(a)) are associated with multiple forms of cardiovascular disease. Lp(a) consists of an apoB 100 -containing particle attached to the plasminogen homologue apo(a). The pathways for Lp(a) clearance are not well understood. We previously discovered that the plasminogen receptor PlgRKT (plasminogen receptor with a C-terminal lysine) promoted Lp(a) uptake in liver cells. Here, we aimed to further define the role of PlgRKT and to investigate the role of 2 other plasminogen receptors, annexin A2 and S100A10 (S100 calcium-binding protein A10) in the endocytosis of Lp(a). METHODS: Human hepatocellular carcinoma (HepG2) cells and haploid human fibroblast-like (HAP1) cells were used for overexpression and knockout of plasminogen receptors. The uptake of Lp(a), LDL (low-density lipoprotein), apo(a), and endocytic cargos was visualized and quantified by confocal microscopy and Western blotting. RESULTS: The uptake of both Lp(a) and apo(a), but not LDL, was significantly increased in HepG2 and HAP1 cells overexpressing PlgRKT, annexin A2, or S100A10. Conversely, Lp(a) and apo(a), but not LDL, uptake was significantly reduced in HAP1 cells in which PlgRKT and S100A10 were knocked out. Surface binding studies in HepG2 cells showed that overexpression of PlgRKT, but not annexin A2 or S100A10, increased Lp(a) and apo(a) plasma membrane binding. Annexin A2 and S100A10, on the other hand, appeared to regulate macropinocytosis with both proteins significantly increasing the uptake of the macropinocytosis marker dextran when overexpressed in HepG2 and HAP1 cells and knockout of S100A10 significantly reducing dextran uptake. Bringing these observations together, we tested the effect of a PI3K (phosphoinositide-3-kinase) inhibitor, known to inhibit macropinocytosis, on Lp(a) uptake. Results showed a concentration-dependent reduction confirming that Lp(a) uptake was indeed mediated by macropinocytosis. CONCLUSIONS: These findings uncover a novel pathway for Lp(a) endocytosis involving multiple plasminogen receptors that enhance surface binding and stimulate macropinocytosis of Lp(a). Although the findings were produced in cell culture models that have limitations, they could have clinical relevance since drugs that inhibit macropinocytosis are in clinical use, that is, the PI3K inhibitors for cancer therapy and some antidepressant compounds.

Objective Preoperative exercise training, or prehabilitation, aims to optimize cardiorespiratory fitness before surgery to reduce the risk of adverse perioperative events and delayed recovery. However, traditional exercise such as walking and cycling can be difficult for people with degenerative joint diseases of the lower limbs, such as osteoarthritis. The purpose of this study was to compare the effect of three low‐impact interventions on cardiorespiratory fitness, physical function, and subjective health before total hip or knee arthroplasty. Methods This was a randomized controlled trial involving 93 participants with severe knee or hip osteoarthritis awaiting joint replacement surgery. Participants underwent cardiopulmonary exercise testing (to measure peak oxygen consumption [O 2 ]), then were randomized to heat therapy (Heat; 20–30 min immersed in 40°C water followed by ~15 min light‐resistance exercise), high‐intensity interval training (HIIT; 6–8 × 60 s intervals on a cross‐trainer or arm ergometer at ~90%–100% peak O 2 ), or home‐based exercise (Home; ~15 min light‐resistance exercise); for up to 36 sessions (3 sessions per week for 12 weeks). Results Peak O 2 increased by 16% across HIIT and to a greater extent than Heat (+2.5 mL × min −1 × kg −1 [95% CI: 0.5–4.4], P = 0.009) and Home (+3.2 mL × min −1 × kg ‐1 [1.2–5.2], P = 0.001). The anaerobic threshold increased across HIIT (+1.5 mL × min −1 × kg −1 [0.7–2.3], P < 0.001) and Heat (+1.2 mL × min −1 × kg −1 [0.4–1.9], P = 0.004), but not Home (−0.5 mL × min −1 × kg −1 [−1.3 to 0.3], P = 0.248). Subjective severity of osteoarthritis was unchanged with any intervention ( P ≥ 0.250). Conclusion Heat therapy and HIIT improved indices of cardiorespiratory fitness preoperatively in patients who have difficulty performing lower‐limb exercise. image

Objective The recommended duration of dual anti-platelet therapy (DAPT) following acute coronary syndrome (ACS) varies from 1 month to 1 year depending on the balance of risks of ischaemia and major bleeding. We designed paired ischaemic and major bleeding risk scores to inform this decision. Methods New Zealand (NZ) patients with ACS investigated with coronary angiography are recorded in the All NZ ACS Quality Improvement registry and linked to national health datasets. Patients were aged 18–84 years (2012–2020), event free at 28 days postdischarge and without atrial fibrillation. Two 28-day to 1-year postdischarge multivariable risk prediction scores were developed: (1) cardiovascular mortality/rehospitalisation with myocardial infarction or ischaemic stroke (ischaemic score) and (2) bleeding mortality/rehospitalisation with bleeding (bleeding score). Findings In 27 755 patients, there were 1200 (4.3%) ischaemic and 548 (2.0%) major bleeding events. Both scores were well calibrated with moderate discrimination performance (Harrell’s c-statistic 0.75 (95% CI, 0.74 to 0.77) and 0.69 (95% CI, 0.67 to 0 .71), respectively). Applying these scores to the 2020 European Society of Cardiology ACS antithrombotic treatment algorithm, the 31% of the cohort at elevated (>2%) bleeding and ischaemic risk would be considered for an abbreviated DAPT duration. For those at low bleeding risk, but elevated ischaemic risk (37% of the cohort), prolonged DAPT may be appropriate, and for those with low bleeding and ischaemic risk (29% of the cohort) short duration DAPT may be justified. Conclusion We present a pair of ischaemic and bleeding risk scores specifically to assist clinicians and their patients in deciding on DAPT duration beyond the first month post-ACS.

Exercise is painful and difficult to perform for patients with severe lower-limb osteoarthritis; consequently, reduced physical activity contributes to increased cardiometabolic disease risk. The aim of this study was to characterize the acute and adaptive cardiovascular and metabolic effects of two low or no impact therapies in patients with severe lower-limb osteoarthritis: passive heat therapy (Heat) and high-intensity interval training (HIIT) utilizing primarily the unaffected limbs, compared to a control intervention of home-based exercise (Home). Participants completed up to 12 weeks of either Heat (20-30 min immersed in 40 degrees C water followed by similar to 15-min light resistance exercise), HIIT (6-8 x 60-s intervals on a cross-trainer or arm ergometer at similar to 90-100% peak (V)overdotO(2)) or Home (similar to 15-min light resistance exercise); all 3 sessions/week. Reductions in systolic (12 & 10 mm Hg), diastolic (7 & 4 mm Hg), and mean arterial (8 & 6 mm Hg) blood pressure (BP) were observed following one bout of Heat or HIIT exposure, lasting for the duration of the 20-min monitoring period. Across the interventions (i.e., 12 weeks), resting systolic BP and diastolic BP decreased with Heat (-9 & -4 mm Hg; p < 0.001) and HIIT (-7 & -3 mm Hg; p <= 0.011), but not Home (0 & 0 mm Hg; p >= 0.785). The systolic and diastolic BP responses to an acute exposure of Heat or HIIT in the first intervention session were moderately correlated with adaptive responses across the intervention (r >= 0.54, p <= 0.005). Neither intervention improved indices of glycemic control (p = 0.310). In summary, both Heat and HIIT induced potent immediate and adaptive hypotensive effects, and the acute response was moderately predictive of the long-term response.

e19074 Background: Hypomethylating agents (HMA) such as decitabine and azacitidine are frontline therapies for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Limited data exist on subsequent cardiovascular (CV) events. Johnson et al. reported 170 patients receiving HMA + venetoclax with a CV event rate of 20%. Aims: To investigate the incidence of CV events in patients receiving HMA. Methods: We analyzed adult AML and MDS patients with > 1 dose of azacitidine or decitabine from 1/2018-12/2020. New CV events were defined as new atrial fibrillation, acute coronary syndrome, cardiomyopathy, congestive heart failure, myocarditis, or pericarditis. Competing risks regression identified baseline predictors associated with time to first CV event while accounting for the competing event of death. Results: 94 patients with no CV history were evaluated which consisted of a mean age 69 +/- 12 years and 50% male. 56% had MDS and 44% AML. Patients with BMI ≥ 30 accounted for 38.3% of the sample. 44 (47%) patients had baseline echocardiogram assessments prior to initiation of HMA with EF of 61+/- 8%; 57 (61%) had a documented prescription of beta-blocker, ACE-I, or ARB at time of HMA initiation. In the 94 patients, 16 new cardiac events occurred. Median survival after therapy initiation was 14.8 months. In a competing risks univariate analysis, lower prior EF (after adjusting for no EF performed) and absence of pre-chemotherapy beta-blocker, ACE-I, or ARB were significantly associated with having a new cardiac event post chemotherapy start (hazard ratio per 5-unit decrease = 1.62 (1.33-1.99), p<0.01 and HR=2.89 (1.08-7.77), p=0.03, respectively). Baseline BMI did not affect risk of a new CV event on HMA therapy (HR per 5 units=1.08 (0.78-1.50), p=0.63). Total HMA dose did not show significance as a predictor for CV events (HR=0.99 (0.987-1.009), p=0.72). Conclusions: We observed a CV event incidence of 19% at 3 years after the start of HMAs. Among patients receiving HMA chemotherapy, those with a lower baseline EF and those not on beta-blocker, ACE-I or ARB therapy prior to initiation of HMA had a higher incidence of cardiotoxicity. Neither pre-HMA BMI nor total HMA dose received appeared to predict risk for CV events. Further research is warranted evaluating the association between HMAs and cardiotoxicity. [Table: see text]