The Prognostic Value of Right Ventricular Function in Patients with Chronic Heart Failure-A Prospective Study.

Background: In patients with stable chronic heart failure with a reduced ejection fraction (HFrEF), left ventricular ejection fraction (LVEF) provides limited prognostic value, especially in patients with moderately to severely reduced LVEF. Echocardiographic parameters of right ventricular function may be associated with adverse clinical events in these patients. Therefore, we analyzed 164 patients with HFrEF in a prospective single-center cohort study to evaluate whether the parameters of right ventricular function are associated with worsening heart failure (WHF) hospitalizations, cardiovascular and all-cause deaths and combined endpoints. Methods: Echocardiographic cine loops were analyzed using vendor-independent post-processing software. Multivariate Cox regression analyses were performed, which were then adjusted for clinical characteristics and left ventricular functional parameters. Results: In these models, higher tricuspid annular plane systolic excursion (TAPSE) was significantly associated with lower rates of WHF hospitalizations (HR 0.880, 95%CI 0.800-0.968, p = 0.008), a composite endpoint of WHF hospitalizations and cardiovascular death (HR 0.878, 95%CI 0.800-0.964, p = 0.006), and a composite endpoint of WHF hospitalization and all-cause death (HR 0.918, 95%CI 0.853-0.988, p = 0.023). These associations were more pronounced in patients with LVEF ≤ 35%. Conclusions: In conclusion, in patients with HFrEF, TAPSE is an independent prognosticator for adverse clinical outcomes, warranting further studies to elucidate whether incorporating TAPSE into established risk scores improves their diagnostic accuracy.

Ketone body levels and its associations with cardiac markers following an acute myocardial infarction: a post hoc analysis of the EMMY trial.

BACKGROUND: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have been suggested to exert cardioprotective effects in patients with heart failure, possibly by improving the metabolism of ketone bodies in the myocardium. METHODS: This post hoc analysis of the EMMY trial investigated the changes in serum ß-hydroxybutyrate (3-ßOHB) levels after acute myocardial infarction (AMI) in response to 26-week of Empagliflozin therapy compared to the usual post-MI treatment. In addition, the association of baseline and repeated measurements of 3-ßOHB with cardiac parameters and the interaction effects of Empagliflozin were investigated. Cardiac parameters included N-terminal pro-B-type natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), left ventricle end-systolic volume (LVESV), left ventricle end-diastolic volume (LVEDV), and left ventricular filling pressure (E/é ratio). RESULTS: The mean 3-ßOHB levels increased from baseline (46.2 ± 3.0 vs. 51.7 ± 2.7) to 6 weeks (48.8 ± 2.2 vs. 42.0 ± 2.3) and 26 weeks (49.3 ± 2.2 vs. 35.8 ± 1.9) in the Empagliflozin group compared to a consistent decline in placebo over 26 weeks (pinteraction < 0.001). Baseline and longitudinal measurements of 3-ßOHB were not significantly associated with NT-proBNP and E/é ratio. Baseline 3-ßOHB value was negatively associated with LVEF (coefficient: - 0.464, 95%CI - 0.863;- 0.065, p = 0.023), while an increase in its levels over time was positively associated with LVEF (0.595, 0.156;1.035, 0.008). The baseline 3-ßOHB was positively associated with LVESV (1.409, 0.186;2.632, 0.024) and LVEDV (0.640, - 1.170;- 2.449, 0.488), while an increase in its levels over time was negatively associated with these cardiac parameters (LVESV: - 2.099, - 3.443;- 0.755, 0.002; LVEDV: - 2.406, - 4.341;- 0.472, 0.015). Empagliflozin therapy appears to modify the association between 3-ßOHB, LVEF (pinteraction = 0.090), LVESV (pinteraction = 0.134), and LVEDV (pinteraction = 0.168), particularly at 26 weeks; however, the results were not statistically significant. CONCLUSION: This post hoc analysis showed that SGLT2i increased 3-ßOHB levels after AMI compared to placebo. Higher baseline 3-ßOHB levels were inversely associated with cardiac function at follow-up, whereas a sustained increase in 3-ßOHB levels over time improved these markers. This highlights the importance of investigating ketone body metabolism in different post-MI phases. Although more pronounced effect of 3-ßOHB on cardiac markers was observed in the SGLT2i group, further research is required to explore this interaction effect.

Impact of the Timing of Mechanical Circulatory Support on the Outcomes in Myocardial Infarction-Related Cardiogenic Shock: Subanalysis of the PREPARE CS Registry.

(1) Background: Mechanical circulatory support (MCS) in myocardial infarction-associated cardiogenic shock is subject to debate. This analysis aims to elucidate the impact of MCS's timing on patient outcomes, based on data from the PREPARE CS registry. (2) Methods: The PREPARE CS prospective registry includes patients who experienced cardiogenic shock (SCAI classes C-E) and were subsequently referred for cardiac catheterization. Our present analysis included a subset of this registry, in whom MCS was used and who underwent coronary intervention due to myocardial infarction. Patients were categorized into an Upfront group and a Procedural group, depending on the timing of MCS's introduction in relation to their PCI. The endpoint was in-hospital mortality. (3) Results: In total, 71 patients were included. MCS was begun prior to PCI in 33 (46%) patients (Upfront), whereas 38 (54%) received MCS during or after the initiation of PCI (Procedural). The groups' baseline characteristics and hemodynamic parameters were comparable. The Upfront group had a higher utilization of the Impella® device compared to extracorporeal membrane oxygenation (67% vs. 33%), while the Procedural group exhibited a balanced use of both (50% vs. 50%). Most patients suffered from multi-vessel disease in both groups (82% vs. 84%, respectively; p = 0.99), and most patients required a complex PCI procedure; the latter was more prevalent in the Upfront group (94% vs. 71%, respectively; p = 0.02). Their rates of complete revascularization were comparable (52% vs. 34%, respectively; p = 0.16). Procedural CPR was significantly more frequent in the Procedural group (45% vs. 79%, p < 0.05); however, in-hospital mortality was similar (61% vs. 79%, respectively; p = 0.12). (4) Conclusions: The upfront implantation of MCS in myocardial infarction-associated CS did not provide an in-hospital survival benefit.

Prevalence and prognostic impact of bone disease in chronic heart failure with reduced ejection fraction.

AIMS: Chronic heart failure is associated with a bone-catabolic state and increases the risk of osteoporosis and fractures. Prospective studies investigating the clinical relevance of bone disease in heart failure are lacking. We aimed to assess the prevalence and prognostic impact of osteoporosis and vertebral fractures (VFs) in chronic heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Symptomatic outpatients with chronic heart failure and a previous diagnosis of overtly reduced left ventricular ejection fraction < 40% on stable, optimal HFrEF therapy and left ventricular ejection fraction < 50% at enrolment were included into a prospective single-centre study. Osteoporosis was determined with dual-energy X-ray absorptiometry and defined as a T-score ≤ 2.5 at any site. VFs were assessed using X-ray of both thoracic and lumbar spine applying the semiquantitative Genant score. We enrolled 205 patients (22% women), with a median age of 66 (IQR 58-74) years. Median left ventricular ejection fraction was 37 (IQR 30-43) % and median N-terminal pro B-type natriuretic peptide was 964 (IQR 363-2173) pg/mL. Osteoporosis, as defined by bone mineral density, and at least one VF were prevalent in 31 (15%) and 29 patients (14%). Osteoporosis or VF were present in 55 patients (27%) and 5 patients (2%) had both osteoporosis and a VF. During a median follow-up of 4.7 (IQR 4.0-5.3) years, 18 patients (9%) died due to cardiovascular (CV) cause, and 46 patients (22%) had a worsening heart failure (WHF) hospitalization. In multivariate Cox regression analyses, presence of VF independently predicted CV death (HR 2.82, 95% CI 1.04-7.65, P = 0.042), WHF hospitalizations (HR 2.39, 95% CI 1.18-4.82, P = 0.015), and a composite endpoint of CV death and WHF hospitalizations (HR 2.44, 95% CI 1.23-4.82, P = 0.011). Osteoporosis was not significantly associated with CV events. CONCLUSIONS: In a prospective study, bone disease affected every fourth patient with HFrEF, and patients with VF at baseline had a two-fold risk of subsequent CV death or WHF hospitalization. Prevalent bone disease, particularly VF, should be considered as a clinically relevant comorbidity in HFrEF.

Impact of the evaluation method on 4D flow-derived diastolic transmitral and myocardial peak velocities: Comparison with echocardiography.

PURPOSE: To compare agreement of different evaluation methods of magnetic resonance (MR) 4D flow-derived diastolic transmitral and myocardial peak velocities as well as their ratios, using echocardiography as reference. METHODS: In this prospective study, 60 subjects without symptoms of cardiovascular disease underwent echocardiography and non-contrast 3 T MR 4D flow imaging of the heart. Early- (E) and late-diastolic (A) transmitral peak filling velocities were evaluated from 4D flow data using three different strategies: 1) at the mitral valve tips in short-axis orientation (SA-method), 2) between the mitral valve tips in 4-chamber orientation (4-chamber-method), and 3) as maximal velocities in the transmitral inflow volume (max-velocity-method). Septal, lateral and average early-diastolic myocardial peak velocities (e') were derived from the myocardial tissue in the vicinity of the mitral valve. 4D flow parameters were compared with echocardiography by correlation and Bland-Altman analysis. RESULTS: All 4D flow-derived E, A and E/A values correlated with echocardiography (r = 0.65-0.73, 0.75-0.83 and 0.74-0.86, respectively). While the SA- and 4-chamber-methods substantially underestimated E and A compared to echocardiography (p < 0.001), the max-velocity-method provided E (p = 0.13) and E/A (p = 0.07) without significant bias. Septal, lateral and average e' from 4D flow as well as the max-velocity-method-derived E/e' correlated with echocardiographic measurements (r = 0.64-0.81) and showed no significant bias (p = 0.26-0.54). CONCLUSION: MR 4D flow imaging allows precise and accurate evaluation of transmitral and myocardial peak velocities for characterization of LV diastolic function without significant bias to echocardiography, when transmitral velocities are assessed from the transmitral inflow volume. This enables the use of validated echocardiography threshold values.

Effects of empagliflozin in women and men with acute myocardial infarction: An analysis from the EMMY trial.

OBJECTIVE: Women have a higher comorbidity burden and a lower survival rate after acute myocardial infarction (AMI) than men. This analysis aimed to investigate the impact of sex on the effect of treatment with the sodium glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin immediately after an AMI. METHODS: Participants were randomized to either empagliflozin or placebo and followed for 26 weeks after initiating the treatment no later than 72 hours after a percutaneous coronary intervention following an AMI. We analyzed the impact of sex on the beneficial effects of empagliflozin observed for heart failure biomarkers as well as structural and functional cardiac parameters. RESULTS: Women had higher NT-proBNP levels at baseline (median 2117pg/mL, IQR 1383-3267 pg/mL versus 1137 pg/mL, IQR 695-2050 pg/mL; p < 0.001) and were older than men (median 61y, IQR 56-65y versus 56y, IQR 51-64y, p = 0.005). The beneficial effects of empagliflozin on NT-proBNP levels (Pinteraction = 0.984), left ventricular ejection fraction (Pinteraction = 0.812), left ventricular end systolic volume (Pinteraction = 0.183), or left ventricular end diastolic volume (Pinteraction = 0.676) were independent of sex. CONCLUSIONS: Empagliflozin exhibited similar benefits in women and men when administered immediately after an AMI.

Low-grade systemic inflammation and left ventricular dysfunction in hypertensive compared to non-hypertensive hypertrophic cardiomyopathy.

BACKGROUND: Arterial hypertension (HTN) is associated with excess mortality in hypertrophic cardiomyopathy (HCM), but underlying mechanisms are largely elusive. The objective of this study was to investigate the association between HTN and markers of left ventricular (LV) dysfunction and low-grade systemic inflammation in a HCM cohort. METHODS: This was a single-center cross-sectional case-control study comparing echocardiographic and plasma-derived indices of LV dysfunction and low-grade systemic inflammation between 30 adult patients with HCM and HTN (HTN+) and 30 sex- and age-matched HCM patients without HTN (HTN-). Echocardiographic measures were assessed using post-processing analyses by blinded investigators. RESULTS: Mean age of the study population was 55.1 ± 10.4 years, 30% were women. Echocardiographic measures of systolic and diastolic dysfunction, including speckle-tracking derived parameters, did not differ between HTN+ and HTN-. Moreover, levels of N-terminal pro B-type natriuretic peptide were balanced between cases and controls. Compared with HTN-, HTN+ patients exhibited a higher white blood cell count [8.1 ± 1.8 109/l vs. 6.4 ± 1.6 109/l; p < 0.001] as well as higher plasma levels of interleukin-6 [2.8 pg/ml (2.0, 5.4) vs. 2.1 pg/ml (1.5, 3.4); p = 0.008] and high-sensitivity C-reactive protein [2.6 mg/l (1.4, 6.5) vs. 1.1 mg/l (0.9, 2.4); p = 0.004]. CONCLUSION: This study demonstrates that HTN is associated with indices of low-grade systemic inflammation among HCM patients. Moreover, this analysis indicates that the adverse impact of HTN in HCM patients is a consequence of systemic effects rather than alterations of cardiac function, as measures of LV systolic and diastolic dysfunction did not differ between HTN+ and HTN-.

Outcomes of ECLS-SHOCK Eligibility Criteria Applied to a Real-World Cohort.

BACKGROUND: Cardiogenic shock (CS) exhibits high (~50%) in-hospital mortality. The recently published Extracorporeal life Support in Cardiogenic Shock (ECLS-SHOCK) trial demonstrated the neutral effects of the use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) on all-cause death, as well as on all secondary outcomes in subjects presenting with myocardial-infarction (MI)-related CS. Here, we compared ECLS-SHOCK eligibility criteria with a real-world cohort of CS patients. METHODS AND RESULTS: ECLS-SHOCK eligibility criteria were applied to a prospective single-center CS registry (the PREPARE CS registry) consisting of 557 patients who were consecutively admitted to the catheterization laboratory (cath lab) of the Medical University of Graz, Austria, due to CS (SCAI C-E). Overall use of mechanical circulatory support (MCS) in this cohort was 19%. Sixty-nine percent of the entire cohort had MI-related CS, 38% of whom would have met ECLS-SHOCK eligibility criteria, thus representing only 27% of the PREPARE CS registry. Exclusion from the ECLS-SHOCK trial was based on patients with initial lactate values below 3 mmol/L (n = 168; 43.6%), aged over 80 years (n = 65; 16.9%), and with a duration of cardiopulmonary resuscitation (CPR) exceeding 45 min (n = 22; 5.7%). The 30-day mortality of patients of the PREPARE CS registry who met the ECLS-SHOCK eligibility criteria was 57.0%, compared to 48.4% of patients in the ECLS-SHOCK trial. The patients' baseline characteristics, however, differed considerably with respect to type of infarction, age, and gender. CONCLUSIONS: In a real-world cohort of patients with MI-related CS, only 38% of patients met the eligibility criteria of the ECLS-SHOCK trial. Thus, the impact of the use of VA-ECMO on outcome parameters in MI-related CS, as observed in the ECLS-SHOCK trial, may differ in a more heterogeneous real-world CS population of the PREPARE CS registry.

MR 4D flow-derived left atrial acceleration factor for differentiating advanced left ventricular diastolic dysfunction.

OBJECTIVES: The magnetic resonance (MR) 4D flow imaging-derived left atrial (LA) acceleration factor α was recently introduced as a means to non-invasively estimate LA pressure. We aimed to investigate the association of α with the severity of left ventricular (LV) diastolic dysfunction using echocardiography as the reference method. METHODS: Echocardiographic assessment of LV diastolic function and 3-T cardiac MR 4D flow imaging were prospectively performed in 94 subjects (44 male/50 female; mean age, 62 ± 12 years). LA early diastolic peak outflow velocity (vE), systolic peak inflow velocity (vS), and early diastolic peak inflow velocity (vD) were evaluated from 4D flow data. α was calculated from α = vE / [(vS + vD) / 2]. Mean parameter values were compared by t-test; diagnostic performance of α in predicting diastolic (dys)function was investigated by receiver operating characteristic curve analysis. RESULTS: Mean α values were 1.17 ± 0.14, 1.20 ± 0.08, 1.33 ± 0.15, 1.77 ± 0.18, and 2.79 ± 0.69 for grade 0 (n = 51), indeterminate (n = 9), grade I (n = 13), grade II (n = 13), and grade III (n = 8) LV diastolic (dys)function, respectively. α differed between subjects with non-advanced (grade < II) and advanced (grade ≥ II) diastolic dysfunction (1.20 ± 0.15 vs. 2.16 ± 0.66, p < 0.001). The area under the curve (AUC) for detection of advanced diastolic dysfunction was 0.998 (95% CI: 0.958-1.000), yielding sensitivity of 100% (95% CI: 84-100%) and specificity of 99% (95% CI: 93-100%) at cut-off α ≥ 1.58. The AUC for differentiating grade III diastolic dysfunction was also 0.998 (95% CI: 0.976-1.000) at cut-off α ≥ 2.14. CONCLUSION: The 4D flow-derived LA acceleration factor α allows grade II and grade III diastolic dysfunction to be distinguished from non-advanced grades as well as from each other. CLINICAL RELEVANCE STATEMENT: As a single continuous parameter, the 4D flow-derived LA acceleration factor α shows potential to simplify the multi-parametric imaging algorithm for diagnosis of advanced LV diastolic dysfunction, thereby identifying patients at increased risk for cardiovascular events. KEY POINTS: • Detection of advanced diastolic dysfunction is typically performed using a complex, multi-parametric approach. • The 4D flow-derived left atrial acceleration factor α alone allows accurate detection of advanced left ventricular diastolic dysfunction. • As a single continuous parameter, the left atrial acceleration factor α could simplify the diagnosis of advanced diastolic dysfunction.

Timing of SGLT2i initiation after acute myocardial infarction.

BACKGROUND: Pharmacological post-MI treatment is routinely initiated at intensive/cardiac care units. However, solid evidence for an early start of these therapies is only available for dual platelet therapy and statins, whereas data on beta blockers and RAAS inhibitors are heterogenous and mainly limited to STEMI and heart failure patients. Recently, the EMMY trial provided the first evidence on the beneficial effects of SGLT2 inhibitors (SGLT2i) when initiated early after PCI. In patients with type 2 diabetes mellitus, SGLT2i are considered "sick days drugs" and it, therefore, remains unclear if very early SGLT2i initiation following MI is as safe and effective as delayed initiation. METHODS AND RESULTS: The EMMY trial evaluated the effect of empagliflozin on NT-proBNP and functional and structural measurements. Within the Empagliflozin group, 22 (9.5%) received early treatment (< 24 h after PCI), 98 (42.2%) within a 24 to < 48 h window (intermediate), and 111 (48.1%) between 48 and 72 h (late). NT-proBNP levels declined by 63.5% (95%CI: - 69.1; - 48.1) in the early group compared to 61.0% (- 76.0; - 41.4) in the intermediate and 61.9% (- 70.8; - 45.7) in the late group (n.s.) within the Empagliflozin group with no significant treatment groups-initiation time interaction (pint = 0.96). Secondary endpoints of left ventricular function (LV-EF, e/e`) as well as structure (LVESD and LVEDD) were also comparable between the groups. No significant difference in severe adverse event rate between the initiation time groups was detected. CONCLUSION: Very early administration of SGLT2i after acute myocardial infarction does not show disadvantageous signals with respect to safety and appears to be as effective in reducing NT-proBNP as well as improving structural and functional LV markers as initiation after 2-3 days.

Impact of the SGLT2-inhibitor empagliflozin on inflammatory biomarkers after acute myocardial infarction - a post-hoc analysis of the EMMY trial.

BACKGROUND: SGTL2-inhibitors are a cornerstone in the treatment of heart failure, but data on patients with acute myocardial infarction (AMI) is limited. The EMMY trial was the first to show a significant reduction in NTproBNP levels as well as improved cardiac structure and function in post-AMI patients treated with Empagliflozin compared to placebo. However, data on the potential impact of SGLT2-inhibitors on inflammatory biomarkers after AMI are scarce. MATERIALS AND METHODS: The EMMY trial is an investigator-initiated, multicentre, double-blind, placebo-controlled trial, which enrolled patients after AMI, receiving either 10 mg Empagliflozin once daily or placebo over a period of 26 weeks on top of standard guideline-recommended therapy starting within 72 h after percutaneous coronary intervention. In this post-hoc subgroup analysis of the EMMY trial, we investigated inflammatory biomarkers of 374 patients. The endpoints investigated were the mean change in inflammatory biomarkers such as high-sensitive c-reactive protein (hsCRP), interleukin-6 (IL-6), neutrophils, leukocytes, neutrophile/lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) from baseline to 26 weeks. RESULTS: Baseline median (interquartile ranges) IL-6 was 17.9 pg/mL (9.0-38.7), hsCRP 18.9 mg/L (11.2-37.1), neutrophil count 7.9 x G/L (6.2-10.1), leukocyte count 10.8 x G/L (9.1-12.8) and neutrophile/lymphocyte ratio (NLR) of 0.74 (0.67-0.80). At week 26, a significant mean reduction in inflammatory biomarkers was observed, being 35.1 ± 3.2% (p < 0.001) for IL-6, 57.4 ± 0.7% (p < 0.001) for hsCRP, 26.1 ± 0.7% (p < 0.001) for neutrophils, 20.5 ± 0.6% (p < 0.001) for leukocytes, 10.22 ± 0.50% (p < 0.001) for NLR, and - 2.53 ± 0.92% for PLR (p = 0.006) with no significant difference between Empagliflozin and placebo treatment. CONCLUSION: Trajectories of inflammatory biomarkers showed a pronounced decline after AMI, but Empagliflozin treatment did not impact this decline indicating no central role in blunted systemic inflammation mediating beneficial effects.

Non-eligibility for pivotal HFpEF/HFmrEF outcome trials and mortality in a contemporary heart failure cohort.

Pivotal outcome trials targeting heart failure with preserved (HFpEF) and mildly-reduced ejection fraction (HFmrEF) may have excluded patients at highest risk of poor outcomes. We aimed to assess eligibility for HFpEF/HFmrEF outcome trials in an unselected heart failure cohort and its association with all-cause mortality. Among 32.028 patients presenting to a tertiary care center emergency unit for any reason between August 2018 and July 2019, we identified 407 admissions with evident HFpEF and HFmrEF. Eligibility criteria for pivotal trials CHARM-Preserved, I-PRESERVE, TOPCAT, PARAGON-HF, EMPEROR-Preserved and DELIVER were assessed by chart review. The proportions of admissions fulfilling HFpEF/HFmrEF trial eligibility criteria were 88% for CHARM-Preserved, 40% for I-PRESERVE, 35% for TOPCAT, 28% for PARAGON-HF, 51% for EMPEROR-Preserved, and 49% for DELIVER. During a median follow-up of 1.9 years, death-from-any-cause occurred in 121 cases (30%). Twenty-four-month overall survival estimates for non-eligible and eligible admissions were 53% vs. 76% for CHARM-Preserved (HR=2.32, 95% CI: 1.47-3.67, p<0.001), 62% vs. 87% for I-PRESERVE (HR=2.97, 1.85-4.77, p<0.001), 67% vs. 84% for TOPCAT (HR=2.04, 1.29-3.24, p = 0.002), 68% vs. 85% for PARAGONHF (HR=2.28, 1.33-3.90, p = 0.003), 64% vs. 81% for EMPEROR-Preserved (HR=1.90, 1.27-2.84, p = 0.002), and 65% vs. 80% for DELIVER (HR=1.71, 1.14-2.57, p = 0.010). Exclusion criteria independently predicting death were eGFR <20 ml/min/1.73 m2, COPD with home oxygen therapy, and severe valvular heart disease. Conclusively, in a contemporary HFpEF/HFmrEF cohort, non-eligibility for outcome trials predicted for strongly increased mortality. HFpEF/HFmrEF patients at highest mortality risk were likely underrepresented in previous outcome trials and their treatment remains an unmet medical need.

AMH in Males: Effects of Body Size and Composition on Serum AMH Levels.

Serum concentrations of anti-Müllerian hormone (AMH) have been found to decrease with increasing body mass index (BMI) in many studies. It is not yet clear whether this stems from an adverse effect of adiposity on AMH production, or from dilution due to the greater blood volume that accompanies a larger body size. To investigate a possible hemodilution effect, we explored the relationships between serum AMH levels and different parameters of body composition using linear regression models in a cohort of adult males. Body weight, lean mass (LM), and body surface area (BSA) were found to be better predictors of AMH than measures of adiposity, such as BMI or fat mass. Since both LM and BSA correlate with plasma volume better than adipose tissue, we conclude that hemodilution of AMH does occur in adult males and should be considered for normalization in future studies.

Alterations in trimethylamine-N-oxide in response to Empagliflozin therapy: a secondary analysis of the EMMY trial.

INTRODUCTION: The relationship between sodium glucose co-transporter 2 inhibitors (SGLT2i) and trimethylamine N-oxide (TMAO) following acute myocardial infarction (AMI) is not yet explored. METHODS: In this secondary analysis of the EMMY trial (ClinicalTrials.gov registration: NCT03087773), changes in serum TMAO levels were investigated in response to 26-week Empagliflozin treatment following an AMI compared to the standard post-MI treatment. Additionally, the association of TMAO changes with clinical risk factors and cardiorenal biomarkers was assessed. RESULTS: The mean age of patients (N = 367) was 57 ± 9 years, 82% were males, and 14% had type 2 diabetes. In the Empagliflozin group, the median TMAO value was 2.62 µmol/L (IQR: 1.81) at baseline, 3.74 µmol/L (2.81) at 6 weeks, and 4.20 µmol/L (3.14) at 26 weeks. In the placebo group, the median TMAO value was 2.90 µmol/L (2.17) at baseline, 3.23 µmol/L (1.90) at 6 weeks, and 3.35 µmol/L (2.50) at 26 weeks. The serum TMAO levels increased significantly from baseline to week 6 (coefficient: 0.233; 95% confidence interval 0.149-0.317, p < 0.001) and week 26 (0.320, 0.236-0.405, p < 0.001). The average increase in TMAO levels over time (pinteraction = 0.007) was significantly higher in the Empagliflozin compared to the Placebo group. Age was positively associated with TMAO, whereas eGFR and LVEF were negatively associated with TMAO. CONCLUSIONS: Our results are contrary to existing experimental studies that showed the positive impact of SGLT2i on TMAO precursors and cardiovascular events. Therefore, we recommend further research investigating the impact of SGLT2i therapy on acute and long-term changes in TMAO in cardiovascular cohorts.

Transesophageal echocardiography-guided versus fluoroscopy-guided patent foramen ovale closure: A single center registry.

BACKGROUND: Percutaneous closure of patent foramen ovale (PFO) is conventionally performed under continuous transesophageal echocardiographic (TEE) guidance. We aimed to evaluate whether a simplified procedural approach, including pure fluoroscopy-guidance and final TEE control, as well as an aimed 'next-day-discharge' is comparable with the conventional TEE-guided procedure in terms of periprocedural and intermediate-term outcomes. METHODS: All patients who underwent a PFO closure at our center between 2010 and 2022 were retrospectively included. Prior to June 2019 cases were performed with continuous TEE guidance (TEE-guided group). Since June 2019, only pure fluoroscopy-guided PFO closures have been performed with TEE insertion and control just prior to device release (fluoroscopy-guided group). We analyzed procedural aspects, as well as long term clinical and echocardiographic outcomes. RESULTS: In total 291 patients were included in the analysis: 197 in the TEE-guided group and 94 in the fluoroscopy-guided group. Fluoroscopy-guided procedures were markedly shorter (48 ± 20 min vs. 25 ± 9 min; p < .01). There was no difference in procedural complications, including death, major bleeding, device dislodgement, stroke or clinically relevant peripheral embolization between the two groups (.5% vs. 0%; p = .99). Hospital stay was also shorter with the simplified approach (2.5 ± 1.6 vs. 3.5 ± 1.2 days; p < .01), allowing 85% same-day discharges during the last 12 months of observation period. At 6 ± 3 months echocardiographic follow-up a residual leakage was described in 8% of the TEE-guided cases and 2% of the fluoroscopy-guided cases (p = .08). CONCLUSION: While a complete TEE-free PFO closure might have potential procedural risks, our approach of pure fluoroscopy-guided with a brisk final TEE check seems to be advantageous in terms of procedural aspects with no sign of any acute or intermediate-term hazard and it could offer an equitable compromise between the two worlds: a complete TEE procedure and a procedure without any TEE.

Automated external defibrillator delivery by drone in mountainous regions to support basic life support - A simulation study.

Background: Out-of-hospital cardiac arrest (OHCA) is associated with poor survival rates. Factors that may enable survival include cardiopulmonary resuscitation (CPR) initiated by bystanders and early use of an automated external defibrillator (AED). This explorative simulation study was conceptualized to test the feasibility of a semi-autonomously operating drone that delivers an AED to a remote emergency location and its bystander-use. Methods: Ten paramedics and nineteen laypersons were confronted with a manikin simulating an OHCA as single bystanders within a field test located in a mountainous region between Austria and Slovenia. The scenario included a mock-call to the local emergency response center that dispatched a drone towards the caller's GPS coordinates and supported the ongoing CPR. The outcomes were the successful delivery of the AED, the time to the first shock, hands-off times, and the overall performance of the CPR. Results: The AED was delivered by drone and used in all 29 scenarios without serious adverse events. The flight time of the drone was in median 5:20 (range: 1:35-8:19) minutes. The paramedics delivered the first shock after a mean of 12:15 ± 2:03 min and hands-off times were 50 ± 22 s. The laypersons delivered the first shock after 14:04 ± 2:10 min and hands-off times were 2:11 ± 0:39 min. All participants felt confident in the handling of the delivered AED. Conclusion: The delivery and usage of an AED via a semi-autonomously flying drone in a remote region is feasible. This approach can lead to early administration of shocks.

Dp-ucMGP as a Biomarker in Sarcopenia.

Sarcopenia is linked with an increased risk of falls, osteoporosis and mortality and is an increasing problem for healthcare systems. No satisfying biomarkers for sarcopenia diagnosis exist, connecting bone, fat and muscle. Matrix-GLA-protein (MGP) is an adipokine that regulates bone metabolism and is associated with decreased muscle strength. Associations of dp-ucMGP were analyzed in the BioPersMed cohort (58 ± 9 years), including 1022 asymptomatic subjects at moderate cardiovascular risk. Serum measurements of dp-ucMGP in 760 persons were performed with the InaKtif MGP Kit with the IDS-iSYS Multi-Discipline Automated System. DXA data (792 persons) measured with the Lunar iDXA system and physical performance data (786 persons) were available. Dp-ucMGP plasma levels correlate with sarcopenia parameters like gait speed (ρ = −0.192, p < 0.001), appendicular skeletal muscle mass (ρ = 0.102, p = 0.005) and appendicular skeletal muscle mass index (ρ = 0.112, p = 0.001). They are lower in persons with sarcopenia (p < 0.001) and higher in persons with reduced physical performance (p = 0.019). Persons in the lowest dp-ucMGP quartile have the highest risk for reduced muscle mass, decreasing with each quartile, whereas persons in the highest quartile have the highest risk of reduced muscle strength. Dp-ucMGP might be a good biomarker candidate in sarcopenia characterization.

Diagnostic Accuracy of Bone Scintigraphy for the Histopathological Diagnosis of Cardiac Transthyretin Amyloidosis-A Retrospective Austrian Multicenter Study.

We aimed to ascertain the real-world diagnostic accuracy of bone scintigraphy in combination with free light chain (FLC) assessment for transthyretin (ATTR) cardiac amyloidosis (CA) using the histopathological diagnosis derived from endomyocardial biopsy (EMB) as a reference standard. We retrospectively analyzed 102 patients (22% women) with suspected CA from seven Austrian amyloidosis referral centers. The inclusion criteria comprised the available results of bone scintigraphy, FLC assessment, and EMB with histopathological analysis. ATTR and AL were diagnosed in 60 and 21 patients (59%, 21%), respectively, and concomitant AL and ATTR was identified in one patient. The specificity and positive predictive value (PPV) of Perugini score ≥ 2 for ATTR CA were 95% and 96%. AL was diagnosed in three out of 31 patients (10%) who had evidence of monoclonal proteins and a Perugini score ≥ 2. When excluding all patients with detectable monoclonal proteins (n = 62) from analyses, the PPV of Perugini score ≥ 2 for ATTR CA was 100% and the NPV of Perugini score < 2 for ATTR CA was 79%. Conclusively, ATTR CA can be diagnosed non-invasively in the case of a Perugini score ≥ 2 and an unremarkable FLC assessment. However, tissue biopsy is mandatory in suspected CA in any other constellation of non-invasive diagnostic work-up.

May Measurement Month 2018-2019: an analysis of blood pressure screening results from Austria.

Arterial hypertension is a global burden leading to over 10.8 million deaths per year worldwide. May Measurement Month (MMM) is a global project initiated by the International Society of Hypertension to raise the awareness of high blood pressure (BP) in the population. Following the MMM protocol 2508 participants ≥18 years had their BP measured in Austria in MMM18 and MMM19. Of those screened, 54.6% were found to be hypertensive, defined as a BP ≥140/90 mmHg and/or being on treatment for hypertension. Among those individuals with hypertension, 56.1% were on medication but only 42.0% of those treated had controlled BP (<140/90 mmHg). Lower BPs were found in those with previous myocardial infarction (MI), probably explained by a medical monitoring system of patients with MI in Austria. Those with hypertension were referred for further medical investigations and were provided lifestyle advice. Among a high number of individuals receiving antihypertensive treatment, BP is still not controlled. Further screening and monitoring of therapeutic effects is urgently required.