Impact of empagliflozin on cardiac structure and function assessed by echocardiography after myocardial infarction: a post-hoc sub-analysis of the emmy trial.

BACKGROUND: Empagliflozin administered after acute myocardial infarction proofed to improve cardiometabolic parameters and biomarkers, but the impact on cardiac function is still largely unknown. The aim of this post-hoc echocardiographic sub-analysis of the EMMY trial was to provide in-depth echocardiographic analysis on the effects of empagliflozin versus placebo on standard and novel echocardiographic structural and functional parameters after acute myocardial infarction. METHODS: In this post-hoc analysis of the EMMY trial a subset of 313 patients (157 empagliflozin vs. 156 placebo) was enrolled for post-processing analysis of echocardiographic structural and functional parameters. On top of two-dimensional and Doppler parameters, myocardial deformation analyses were performed to assess ventricular and atrial strain values. RESULTS: Left ventricular volumes showed significant differences in favor of empagliflozin over the course of the trial (change in left ventricular end-diastolic volume median [interquartile range] 8 [-3;19]% versus 13 [0;29]%, p = 0.048; left ventricular end-systolic volume -3 [-15;12]% versus 4 [-12;18]%, p = 0.044). This effect persisted after adjusting for baseline values, age, and sex. Left ventricular systolic and diastolic function overall improved over the course of the trial and parameters for diastolic function showed a distinct trend between groups but did not meet statistical significance in this cohort. CONCLUSION: In this post-hoc analysis among patients with acute myocardial infarction, treatment with empagliflozin resulted in a significant beneficial effect on left ventricular end-diastolic and end-systolic volume, without significantly improving left ventricular or right ventricular functional parameters compared to placebo after 26 weeks. GOV REGISTRATION: NCT03087773.

Temporal Trends in Takotsubo Syndrome: Results From the International Takotsubo Registry.

BACKGROUND: The perception of takotsubo syndrome (TTS) has evolved significantly over the years, primarily driven by increased recognition of acute complications and mortality. OBJECTIVES: This study aimed to explore temporal trends in demographic patterns, risk factors, clinical presentations, and outcomes in patients with TTS. METHODS: Patients diagnosed with TTS between 2004 and 2021 were enrolled from the InterTAK (International Takotsubo) registry. To assess temporal trends, patients were divided into 6 groups, each corresponding to a 3-year interval within the study period. RESULTS: Overall, 3,957 patients were included in the study. There was a significant demographic transition, with the proportion of male patients rising from 10% to 15% (P = 0.003). Although apical TTS remained the most common form, the diagnosis of midventricular TTS increased from 18% to 28% (P = 0.018). The prevalence of physical triggers increased from 39% to 58% over the years (P < 0.001). There was a significant increase in 60-day mortality over the years (P < 0.001). However, a landmark analysis excluding patients who died within the first 60 days showed no differences in 1-year mortality (P = 0.150). CONCLUSIONS: This study of temporal trends in TTS highlights a transition in patients demographic with a growing prevalence among men, increasing recognition of midventricular TTS type, and increased short-term mortality and rates of cardiogenic shock in recent years. This transition aligns with the rising prevalence of physical triggers, as expression of increased recognition of TTS in association with acute comorbidities.

Ertugliflozin to Reduce Arrhythmic Burden in Patients with ICDs/CRT-Ds.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have beneficial pleiotropic effects, contributing to improved cardiovascular and renal outcomes for patients with and without diabetes. The impact of SGLT2is on arrhythmic burden remains largely unexplored through randomized trials. METHODS: In this multicenter, double-blind, randomized, placebo-controlled trial, we investigated the effects of ertugliflozin on arrhythmic burden among patients with heart failure with an ejection fraction less than 50%. All patients had an implantable cardioverter-defibrillator (ICD) with or without a cardiac resynchronization therapy device (CRT-D) and were randomized (1:1) to receive either ertugliflozin 5 mg once daily or placebo. The primary end point was the number of incident sustained (>30 seconds) ventricular tachycardia or ventricular fibrillation events from baseline to week 52. Secondary end points included the total number of non-sustained ventricular tachycardias, appropriate ICD therapies, changes in N-terminal pro-brain-type natriuretic peptide (NTproBNP) levels, and the number of heart failure hospitalizations. RESULTS: Randomization was prematurely terminated, after class IA guideline recommendations were published for SGLT2is in patients with heart failure regardless of the ejection fraction. The final analysis included 46 patients (11% of the originally planned sample size). The yearly rate of the primary end point was 3.5 (95% confidence interval [CI] 2.8 to 4.4) with ertugliflozin compared with 13.3 with placebo (95% CI 11.8 to 14.8; rate ratio 0.16, 95% CI 0.04 to 0.61; P<0.001). There were no apparent differences in appropriate ICD therapies, hospitalizations, NTproBNP levels, or predefined adverse and serious adverse events. CONCLUSIONS: Ertugliflozin reduced sustained ventricular tachycardia or ventricular fibrillation events in adults with heart failure and an ICD compared with placebo; however, our trial ended early and thus results should be interpreted with caution. (Funded by Investigator-initiated Studies Program of Merck Sharp & Dohme Corp and Pfizer; EudraCT number, 2020-002581-14; ClinicalTrials.gov number NCT04600921.).

Inflammation in Obesity-Related HFpEF: The STEP-HFpEF Program.

BACKGROUND: Inflammation is thought to be an important mechanism for the development and progression of obesity-related heart failure with preserved ejection fraction (HFpEF). In the STEP-HFpEF Program, once-weekly 2.4 mg semaglutide improved heart failure-related symptoms, physical limitations, and exercise function, reduced the levels of C-reactive protein (CRP), a biomarker of inflammation, and reduced body weight in participants with obesity-related HFpEF. However, neither the prevalence nor the clinical characteristics of patients who have various magnitudes of inflammation in the context of obesity-related HFpEF have been well described. Furthermore, whether the beneficial effects of semaglutide on the various HF efficacy endpoints in the STEP-HFpEF Program are modified by the baseline levels of inflammation has not been fully established. Finally, the relationship between weight reduction and changes in CRP across the STEP-HFpEF Program have not been fully defined. OBJECTIVES: This study sought to: 1) evaluate baseline characteristics and clinical features of patients with obesity-related HFpEF that have various levels of inflammation in the STEP-HFpEF Program; 2) determine if the effects of weekly semaglutide 2.4 mg vs placebo across all key outcomes are influenced by baseline levels of inflammation assessed by CRP levels; and 3) determine the relationship between change in CRP and weight loss in the STEP-HFpEF Program. METHODS: This was a secondary analysis of pooled data from 2 international, double-blind, placebo-controlled, randomized trials (STEP-HFpEF and STEP-HFpEF DM). The outcomes were change in the dual primary endpoints (health status [measured by the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS)] and body weight) from baseline to 52 weeks according to baseline CRP levels. Additional efficacy endpoints included change in 6-minute walk distance (6MWD), a hierarchical composite endpoint that included death, heart failure events, and differences in the change in the KCCQ-CSS and 6MWD, and levels of CRP in semaglutide- vs placebo-treated patients. Patients were stratified into 3 categories based on baseline CRP levels (<2, ≥2 to <10, and ≥10 mg/L). RESULTS: In total, 1,145 patients were randomized, of which 71% of patients had evidence of inflammation (CRP ≥2 mg/L). At baseline, those with higher levels of inflammation were younger, were more likely to be female, and had higher body mass index, worse health status (KCCQ-CSS), and shorter 6MWD. Semaglutide vs placebo led to reductions in HF-related symptoms and physical limitations as well as body weight, and to improvements in 6MWD and the hierarchical composite endpoint that were consistent across baseline CRP categories (all P interaction nonsignificant). Semaglutide also reduced CRP to a greater extent than placebo regardless of baseline CRP levels (P interaction = 0.32). Change in CRP from baseline to 52 weeks was similar regardless of the magnitude of weight loss (P interaction = 0.91). CONCLUSIONS: Inflammation is highly prevalent in obesity-related HFpEF. Semaglutide consistently improved HF-related symptoms, physical limitations, and exercise function, and reduced body weight across the categories of baseline CRP. Semaglutide also reduced inflammation, regardless of either baseline CRP or magnitude of weight loss during the trials. (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity [STEP-HFpEF; NCT04788511]; Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes [STEP HFpEF DM; NCT04916470]).

Estimated glomerular filtration rate slope and risk of primary and secondary major adverse cardiovascular events and heart failure hospitalization in people with type 2 diabetes: An analysis of the EXSCEL trial.

AIM: The decline in estimated glomerular filtration rate (eGFR), a significant predictor of cardiovascular disease (CVD), occurs heterogeneously in people with diabetes because of various risk factors. We investigated the role of eGFR decline in predicting CVD events in people with type 2 diabetes in both primary and secondary CVD prevention settings. MATERIALS AND METHODS: Bayesian joint modelling of repeated measures of eGFR and time to CVD event was applied to the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial to examine the association between the eGFR slope and the incidence of major adverse CV event/hospitalization for heart failure (MACE/hHF) (non-fatal myocardial infarction, non-fatal stroke, CV death, or hospitalization for heart failure). The analysis was adjusted for age, sex, smoking, systolic blood pressure, baseline eGFR, antihypertensive and lipid-lowering medication, diabetes duration, atrial fibrillation, high-density cholesterol, total cholesterol, HbA1c and treatment allocation (once-weekly exenatide or placebo). RESULTS: Data from 11 101 trial participants with (n = 7942) and without (n = 3159) previous history of CVD were analysed. The mean ± SD eGFR slope per year in participants without and with previous CVD was -0.68 ± 1.67 and -1.03 ± 2.13 mL/min/1.73 m2, respectively. The 5-year MACE/hHF incidences were 7.5% (95% CI 6.2, 8.8) and 20% (95% CI 19, 22), respectively. The 1-SD decrease in the eGFR slope was associated with increased MACE/hHF risks of 48% (HR 1.48, 95% CI 1.12, 1.98, p = 0.007) and 33% (HR 1.33, 95% CI 1.18,1.51, p < 0.001) in participants without and with previous CVD, respectively. CONCLUSIONS: eGFR trajectories over time significantly predict incident MACE/hHF events in people with type 2 diabetes with and without existing CVD, with a higher hazard ratio for MACE/hHF in the latter group.

Impact of baseline ECG characteristics on changes in cardiac biomarkers and echocardiographic metrices after acute myocardial infarction treated with Empagliflozin.

The EMMY trial was a multicentre, investigator-initiated, placebo-controlled, double-blind trial, which enrolled 476 patients immediately following AMI and the first study demonstrating a significant reduction in NT-proBNP-levels as well as significant improvements in cardiac structure and function in patients after acute myocardial infarction treated with empagliflozin vs. placebo. However, hardly any data are available investigating the prognostic role of baseline electrocardiogram metrics in SGLT2-inhibitor-treated patients. This post-hoc analysis investigated the association of baseline ECG metrics collected in one centre of the trial (181 patients) with changes in structural and functional cardiac parameters as well as cardiac biomarkers in response to Empagliflozin treatment. A total of 181 patients (146 men; mean age 58 ± 14 years) were included. Median PQ-interval was 156 (IQR 144-174) milliseconds (ms), QRS width 92 (84-98) ms, QTc interval 453 (428-478) ms, Q-wave duration 45 (40-60) ms, Q-wave amplitude 0.40 (0.30-0.70) millivolt (mV), and heart rate was 71 (64-85) bpm. For functional cardiac parameters (LVEF and E/e') of the entire cohort, a greater decrease of E/e' from baseline to week 26 was observed in shorter QRS width (P = 0.005).Structural cardiac endpoints were only found to have a significant positive correlation between LVEDD and Q wave duration (P = 0.037). Higher heart rate was significantly correlated with better response in LVEF (P = 0.001), E/e' (P = 0.021), and NT-proBNP (P = 0.005). Empagliflozin-treatment showed no interaction with the results. Baseline ECG characteristics post AMI are neither predictive for beneficial NTproBNP effects of Empagliflozin post AMI, nor for functional or structural changes within 26 weeks post AMI.

Better understanding of c-reactive protein and leukocytes in psychiatric inpatients with affective disorders: A biopsychosocial approach.

BACKGROUND: Affective disorders (AD) have been linked to inflammatory processes, although the underlying mechanisms of this relationship are still not fully elucidated. It is hypothesized that demographic, somatic, lifestyle, and personality variables predict inflammatory parameters in AD. AIM: To identify biopsychosocial factors contributing to inflammation in AD measured with two parameters, C-reactive protein (CRP) and leukocytes. METHODS: This observational study investigated 186 hospital inpatients diagnosed with AD using demographic parameters, serum inflammatory markers, somatic variables, psychological questionnaires, and lifestyle parameters. Hierarchical regression analyses were used to predict inflammatory markers from demographic, somatic, lifestyle, and personality variables. RESULTS: Analyses showed that 33.8% of the variance of CRP was explained by body mass index and other somatic medication (e.g. anti-diabetics), age and education, and age of affective disorder diagnosis. For leukocytes, 20.1% of the variance was explained by smoking, diet, metabolic syndrome (MetS), and anti-inflammatory medication (e.g. non-steroidal anti-inflammatory drugs). Other psychiatric or behavioural variables did not reach significance. CONCLUSION: Metabolic components seem important, with mounting evidence for a metabolic affective disorder subtype. Lifestyle modifications and psychoeducation should be employed to prevent or treat MetS in AD.

Baseline characteristics of patients with heart failure with mildly reduced or preserved ejection fraction: The FINEARTS-HF trial.

AIMS: To describe the baseline characteristics of participants in the FINEARTS-HF trial, contextualized with prior trials including patients with heart failure (HF) with mildly reduced and preserved ejection fraction (HFmrEF/HFpEF). The FINEARTS-HF trial is comparing the effects of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo in reducing cardiovascular death and total worsening HF events in patients with HFmrEF/HFpEF. METHODS AND RESULTS: Patients with symptomatic HF, left ventricular ejection fraction (LVEF) ≥40%, estimated glomerular filtration rate ≥ 25 ml/min/1.73 m2, elevated natriuretic peptide levels and evidence of structural heart disease were enrolled and randomized to finerenone titrated to a maximum of 40 mg once daily or matching placebo. We validly randomized 6001 patients to finerenone or placebo (mean age 72 ± 10 years, 46% women). The majority were New York Heart Association functional class II (69%). The baseline mean LVEF was 53 ± 8% (range 34-84%); 36% of participants had a LVEF <50% and 64% had a LVEF ≥50%. The median N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 1041 (interquartile range 449-1946) pg/ml. A total of 1219 (20%) patients were enrolled during or within 7 days of a worsening HF event, and 3247 (54%) patients were enrolled within 3 months of a worsening HF event. Compared with prior large-scale HFmrEF/HFpEF trials, FINEARTS-HF participants were more likely to have recent (within 6 months) HF hospitalization and greater symptoms and functional limitations. Further, concomitant medications included a larger percentage of sodium-glucose cotransporter 2 inhibitors and angiotensin receptor-neprilysin inhibitors than previous trials. CONCLUSIONS: FINEARTS-HF has enrolled a broad range of high-risk patients with HFmrEF and HFpEF. The trial will determine the safety and efficacy of finerenone in this population.

Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes.

BACKGROUND: Obesity and type 2 diabetes are prevalent in patients with heart failure with preserved ejection fraction and are characterized by a high symptom burden. No approved therapies specifically target obesity-related heart failure with preserved ejection fraction in persons with type 2 diabetes. METHODS: We randomly assigned patients who had heart failure with preserved ejection fraction, a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or more, and type 2 diabetes to receive once-weekly semaglutide (2.4 mg) or placebo for 52 weeks. The primary end points were the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating fewer symptoms and physical limitations) and the change in body weight. Confirmatory secondary end points included the change in 6-minute walk distance; a hierarchical composite end point that included death, heart failure events, and differences in the change in the KCCQ-CSS and 6-minute walk distance; and the change in the C-reactive protein (CRP) level. RESULTS: A total of 616 participants underwent randomization. The mean change in the KCCQ-CSS was 13.7 points with semaglutide and 6.4 points with placebo (estimated difference, 7.3 points; 95% confidence interval [CI], 4.1 to 10.4; P<0.001), and the mean percentage change in body weight was -9.8% with semaglutide and -3.4% with placebo (estimated difference, -6.4 percentage points; 95% CI, -7.6 to -5.2; P<0.001). The results for the confirmatory secondary end points favored semaglutide over placebo (estimated between-group difference in change in 6-minute walk distance, 14.3 m [95% CI, 3.7 to 24.9; P = 0.008]; win ratio for hierarchical composite end point, 1.58 [95% CI, 1.29 to 1.94; P<0.001]; and estimated treatment ratio for change in CRP level, 0.67 [95% CI, 0.55 to 0.80; P<0.001]). Serious adverse events were reported in 55 participants (17.7%) in the semaglutide group and 88 (28.8%) in the placebo group. CONCLUSIONS: Among patients with obesity-related heart failure with preserved ejection fraction and type 2 diabetes, semaglutide led to larger reductions in heart failure-related symptoms and physical limitations and greater weight loss than placebo at 1 year. (Funded by Novo Nordisk; STEP-HFpEF DM ClinicalTrials.gov number, NCT04916470.).

Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials.

BACKGROUND: In the STEP-HFpEF (NCT04788511) and STEP-HFpEF DM (NCT04916470) trials, the GLP-1 receptor agonist semaglutide improved symptoms, physical limitations, bodyweight, and exercise function in people with obesity-related heart failure with preserved ejection fraction. In this prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials, we aimed to provide a more definitive assessment of the effects of semaglutide across a range of outcomes and to test whether these effects were consistent across key patient subgroups. METHODS: We conducted a prespecified pooled analysis of individual patient data from STEP-HFpEF and STEP-HFpEF DM, randomised, double-blind, placebo-controlled trials at 129 clinical research sites in 18 countries. In both trials, eligible participants were aged 18 years or older, had heart failure with a left ventricular ejection fraction of at least 45%, a BMI of at least 30 kg/m2, New York Heart Association class II-IV symptoms, and a Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS; a measure of heart failure-related symptoms and physical limitations) of less than 90 points. In STEP-HFpEF, people with diabetes or glycated haemoglobin A1c concentrations of at least 6·5% were excluded, whereas for inclusion in STEP-HFpEF DM participants had to have been diagnosed with type 2 diabetes at least 90 days before screening and to have an HbA1c of 10% or lower. In both trials, participants were randomly assigned to either 2·4 mg semaglutide once weekly or matched placebo for 52 weeks. The dual primary endpoints were change from baseline to week 52 in KCCQ-CSS and bodyweight in all randomly assigned participants. Confirmatory secondary endpoints included change from baseline to week 52 in 6-min walk distance, a hierarchical composite endpoint (all-cause death, heart failure events, and differences in changes in KCCQ-CSS and 6-min walk distance); and C-reactive protein (CRP) concentrations. Heterogeneity in treatment effects was assessed across subgroups of interest. We assessed safety in all participants who received at least one dose of study drug. FINDINGS: Between March 19, 2021 and March 9, 2022, 529 people were randomly assigned in STEP-HFpEF, and between June 27, 2021 and Sept 2, 2022, 616 were randomly assigned in STEP-HFpEF DM. Overall, 1145 were included in our pooled analysis, 573 in the semaglutide group and 572 in the placebo group. Improvements in KCCQ-CSS and reductions in bodyweight between baseline and week 52 were significantly greater in the semaglutide group than in the placebo group (mean between-group difference for the change from baseline to week 52 in KCCQ-CSS 7·5 points [95% CI 5·3 to 9·8]; p<0·0001; mean between-group difference in bodyweight at week 52 -8·4% [-9·2 to -7·5]; p<0·0001). For the confirmatory secondary endpoints, 6-min walk distance (mean between-group difference at week 52 17·1 metres [9·2 to 25·0]) and the hierarchical composite endpoint (win ratio 1·65 [1·42 to 1·91]) were significantly improved, and CRP concentrations (treatment ratio 0·64 [0·56 to 0·72]) were significantly reduced, in the semaglutide group compared with the placebo group (p<0·0001 for all comparisons). For the dual primary endpoints, the efficacy of semaglutide was largely consistent across multiple subgroups, including those defined by age, race, sex, BMI, systolic blood pressure, baseline CRP, and left ventricular ejection fraction. 161 serious adverse events were reported in the semaglutide group compared with 301 in the placebo group. INTERPRETATION: In this prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials, semaglutide was superior to placebo in improving heart failure-related symptoms and physical limitations, and reducing bodyweight in participants with obesity-related heart failure with preserved ejection fraction. These effects were largely consistent across patient demographic and clinical characteristics. Semaglutide was well tolerated. FUNDING: Novo Nordisk.

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.

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.

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 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.

Special Issue "Coronary Artery Disease Interventions".

The treatment and burden of patients with severe ischemic heart disease, whether acute or chronic, remain some of the greatest challenges in cardiology [...].

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.

Changes in Lipoprotein(a) Levels in People after ST Elevation Myocardial Infarction-The STEMI-Lipids Study.

Lipoprotein(a) (Lp(a)) is considered an independent risk factor for cardiovascular diseases. The plasma concentration of Lp(a) is largely genetically determined but varies over a wide range within the population. This study investigated changes in Lp(a) levels after an acute myocardial infarction. Patients who underwent coronary angiography due to an ST elevation myocardial infarction were enrolled (n = 86), and Lp(a) levels were measured immediately after the intervention, one day, two days, and at a post-discharge follow-up visit at 3 to 6 months after the acute myocardial infarction. Median Lp(a) levels increased from a median of 7.9 mg/dL (3.8-37.1) at hospital admission to 8.4 mg/dL (3.9-35.4) on the following day, then to 9.3 mg/dL (3.7-39.1) on day two (p < 0.001), and to 11.2 mg/dL (4.4-59.6) at the post-discharge follow-up (p < 0.001). Lp(a) levels were the lowest during the acute myocardial infarction and started to increase significantly immediately thereafter, with the highest levels at the post-discharge follow-up. The moderate but significant increase in Lp(a) in people with acute myocardial infarction appears to be clinically relevant on an individual basis, especially when specific Lp(a) cut-off levels are supposed to determine the initiation of future treatment. Hence, a repeated measurement of Lp(a) after myocardial infarction should be performed.