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This study aimed to determine standard left (LV) and right ventricular (RV) transesophageal echocardiographic (TEE) measurements in swine. Additionally, global myocardial work index (GWI) was estimated using pressure-strain loops (PSL). A comprehensive TEE examination was conducted in ten anesthetized, intubated and mechanically ventilated healthy female German landrace swine, weighing 44 to 57 kg. For GWI calculation, we performed LV and RV segmental strain analysis and used invasively measured LV and RV pressure to obtain PSL. The GWI and further myocardial work indices were calculated from the area of the PSL using commercially available software. Furthermore, hemodynamic measurements were obtained using indwelling catheters. We obtained complete standardized baseline values for left and right ventricular dimensions and function. Biplane LV ejection fraction was 63 ± 7 % and the LV end-diastolic volume was 70.5 ± 5.9 ml. Tissue Doppler estimated peak tricuspid annular systolic velocity was 13.1 ± 1.8 cm/s. The Doppler estimated LV and RV stroke volume index were 75.6 ± 7.2 ml/m2 and 76.7 ± 7.8 ml/m2 respectively. Pulsed wave Doppler derived cardiac output correlated well with cardiac output estimated using the thermodilution method (7.0 ± 1.2 l/min vs. 7.0 ± 1.1 l/min, r = 0.812, p = 0.004). The LV global longitudinal strain was -21.3 ± 3.9 % and the RV global longitudinal strain was -15.4 ± 2.5 %. LV GWI was 1885(1281–2121) mmHg*% and 297 ± 62 mmHg*% for the RV. LV global myocardial work efficiency was 82.6 ± 4 % and 83(72–88) % for the RV. TEE offers sufficient morphological, functional and hemodynamic assessment of the heart in swine. Myocardial contractility and mechanics can be reliably evaluated with the non-invasive GWI derived from echocardiography without additional invasive measures.

This study investigates the prognosis of acute decompensated heart failure (ADHF) on admission (i.e., primary ADHF) as compared to ADHF onset during course of hospitalization (i.e., secondary ADHF) in patients hospitalized with heart failure with mildly reduced ejection fraction (HFmrEF). Limited data regarding the prognostic impact of the timing of onset of ADHF is available. Consecutive patients with HFmrEF and ADHF were retrospectively included at one institution from 2016 to 2022. Patients with primary ADHF were compared to patients with secondary ADHF with regard to the primary endpoint all-cause mortality at 30 months. Kaplan–Meier, uni- and multivariable Cox proportional regression analyses were applied for statistics. From a total of 484 patients hospitalized with HFmrEF and ADHF, 67.98% (n = 329) were admitted with primary ADHF. Patients with secondary ADHF had higher rates of concomitant acute myocardial infarction, alongside with a higher extend of coronary artery disease. The risk of all-cause mortality at 30 months was not affected by the timing of ADHF (hazard ratio (HR) = 0.853; 95% confidence interval (CI) 0.653–1.115; p = 0.246). However, patients with primary ADHF were associated with a higher risk of HF-related rehospitalization at 30 months (HR = 2.513; 95% CI 1.555–4.065; p = 0.001), which was still evident after multivariable adjustment (HR = 2.347; 95% CI 1.418–3.883; p = 0.001). The timing of onset of ADHF was not associated with long-term mortality in HFmrEF, however primary ADHF was associated with a higher risk of HF-related rehospitalization.

Evidence regarding potential agent-specific differences among β-blockers in heart failure with mildly reduced ejection fraction (HFmrEF) remains limited. The present study sought to investigate the association of metoprolol versus carvedilol prescribed at hospital discharge with 30-month all-cause mortality and HF-related rehospitalization, and to explore potential effect modification by atrial fibrillation (AF). Consecutive patients hospitalized with HFmrEF between 2016 and 2022 were included. Exposure was β-blocker therapy at discharge (metoprolol succinate or carvedilol). Outcomes were analyzed using Kaplan-Meier estimates, multivariable Cox regression and propensity score matching. Among 2109 patients discharged alive, 1625 (77.5%) received β-blockers (metoprolol = 1033; carvedilol = 283). Carvedilol recipients were younger (median 72 vs. 76 years) and more frequently had prior heart failure (44.2% vs. 33.2%). Thirty-month mortality occurred in 25.5% of metoprolol-treated and 31.8% of carvedilol-treated patients (unadjusted hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.61-0.98; = 0.031). This association was observed in patients without AF, but not in those with AF. After multivariable adjustments, the association remained directionally similar (adjusted HR 0.76, 95% CI 0.58-1.00). In the matched cohort ( = 246 per group), metoprolol was still associated with lower mortality (HR 0.65, 95% CI 0.46-0.93; = 0.017). By contrast, HF-related rehospitalization did not differ significantly between the two groups. In this observational HFmrEF cohort, treatment with metoprolol at index hospital discharge was associated with lower 30-month mortality compared with carvedilol. Given the observational study design in line with the higher burden of comorbidities in patients discharged on carvedilol, further prospective studies are needed to clarify the impact of different β-blocker types in heart failure patients.

Background Cancer cachexia, affecting up to 80% of patients with cancer, is characterized by muscle and fat loss with functional decline. Preclinical research seeks to uncover the molecular mechanisms underlying cachexia to identify potential targets. Housing laboratory mice at ambient temperature induces cold stress, triggering thermogenic activity and metabolic adaptations. Yet, the impact of housing temperature on preclinical cachexia remains unknown. Methods Colon 26 carcinoma (C26)‐bearing and PBS‐inoculated (Ctrl) mice were housed at standard (ST; 20°C–22°C) or thermoneutral temperature (TN; 28°C–32°C). They were monitored for body weight, composition, food intake and systemic factors. Upon necropsy, tissues were weighed and used for evaluation of ex vivo force and respiration, or snap frozen for biochemical assays. Results C26 mice lost 7.5% body weight (p = 0.0001 vs. Ctrls), accounted by decreased fat mass (−35%, p < 0.0001 vs. Ctrls), showing mild cachexia irrespective of housing temperature. All C26 mice exhibited reduced force (−40%, p < 0.0001 vs. Ctrls) and increased atrogene expression (3‐fold, p < 0.003 vs. Ctrls). Cancer altered white adipose tissue (WAT)'s functional gene signature (49%, p < 0.05 vs. Ctrls), whereas housing temperature reduced brown adipose tissue (BAT)'s (−78%, p < 0.05 vs. ST Ctrl). Thermogenic capacity measured by Ucp1 expression decreased upon cancer in both WAT and BAT (−93% and −63%, p < 0.0044 vs. Ctrls). Cancer‐driven glucose intolerance was noted at ST (26%, p = 0.0192 vs. ST Ctrl), but restored at TN (−23%, p = 0.005 vs. ST C26). Circulating FGF21, GDF‐15 and IL‐6 increased in all C26 mice (4‐fold, p < 0.009 vs. Ctrls), with a greater effect on IL‐6 at TN (76%, p = 0.0018 vs. ST C26). Tumour and WAT Il6 mRNA levels remained unchanged, while cancer induced skeletal muscle (SkM) Il6 (2‐fold, p = 0.0016 vs. Ctrls) at both temperatures. BAT Il6 was only induced in C26 mice at TN (116%, p = 0.0087 vs. ST C26). At the bioenergetics level, cancer increased SkM SERCA ATPase activity at ST (4‐fold, p = 0.0108 vs. ST Ctrl) but not at TN. In BAT, O2 consumption enhanced in C26 mice at ST (119%, p < 0.03 vs. ST Ctrl) but was blunted at TN (−44%, p < 0.0001 vs. ST C26). Cancer increased BAT ATP levels regardless of temperature (2‐fold, p = 0.0046 vs. Ctrls), while SERCA ATPase activity remained unchanged at ST and decreased at TN (−59%, p = 0.0213 vs. TN Ctrl). Conclusions In mild cachexia, BAT and SkM bioenergetics are susceptible to different housing temperatures, which influences cancer‐induced alterations in glucose metabolism and systemic responses.

Objectives: To evaluate the long-term prognostic value of left ventricular ejection fraction (LVEF) in consecutive patients undergoing invasive coronary angiography (CA). Background: LVEF is a key prognostic marker in cardiovascular disease, but its value across different clinical indications for CA remains insufficiently characterized. Methods: Consecutive patients undergoing CA between January 2016 and August 2022 were retrospectively included at one institution. Patients were stratified into four LVEF groups: ≥ 55%, 45–54%, 35–44%, and <35%. The primary endpoint was rehospitalization for heart failure (HF) at 36 months. Secondary endpoints were acute myocardial infarction (AMI) and coronary revascularization. Kaplan–Meier and multivariable Cox regression analyses were conducted within the entire study cohort and pre-defined subgroups. Results: A total of 6888 patients were included (median age: 71 years; 65.2% males). LVEF < 35% was associated with a higher comorbidity burden and more extensive coronary artery disease (e.g., three-vessel CAD: 38.6% vs. 20.7%, p < 0.001). Event rates for HF rehospitalization and AMI increased progressively with declining LVEF, while revascularization rates varied across categories. Statistically significant differences across LVEF groups were observed for all three endpoints in unadjusted analyses (log-rank p < 0.001). In multivariable models, LVEF < 35% independently predicted HF rehospitalization (HR = 3.731, p < 0.001) and AMI (HR = 4.184, p < 0.001), but not revascularization (HR = 0.867, p = 0.378). The prognostic association was demonstrated across all subgroups stratified by age, sex, subtype of acute coronary syndrome, and CAD severity. Conclusions: Reduced LVEF is an independent predictor of HF rehospitalization and AMI in patients undergoing coronary angiography, irrespective of its indication, whereas no independent association was observed with coronary revascularization.

Evidence regarding the prognostic impact of angiotensin-converting enzyme inhibitors (ACEi) vs. receptor blockers (ARB) in heart failure with mildly reduced ejection fraction (HFmrEF) is limited. We retrospectively studied consecutive patients hospitalized with HFmrEF from 2016 until 2022 at a German university hospital. The prognostic impact of treatment with ACEi compared with ARB was investigated regarding the primary endpoint of all-cause mortality at 30 months. The key secondary endpoint was heart failure (HF)-related rehospitalization. A total of 1,551 patients discharged on renin-angiotensin system inhibitors (ACEi:  = 1,055; ARB:  = 496) were included. Patients treated with ARB were older and had a higher burden of comorbidities. All-cause mortality at 30 months occurred in 251/1,055 (23.8%) patients treated with ACEi and in 147/496 (29.6%) patients treated with ARB [unadjusted hazard ratio [HR] = 0.762, 95% confidence interval [CI] 0.622-0.934; log-rank  = 0.009]. After multivariable adjustment, ACEi were still associated with improved long-term survival (adjusted HR = 0.786, 95% CI: 0.625-0.989;  = 0.040). This association was still found after propensity score matching (  = 440 per group) (23.2% vs. 29.5%; HR = 0.749, 95% CI: 0.578-0.971;  = 0.029). In contrast, the risk of HF-related rehospitalization at 30 months did not differ between the two groups in the unmatched cohort (12.7% vs. 14.5%; HR = 0.849, 95% CI: 0.638-1.130;  = 0.262) and after propensity score matching (16.1% vs. 14.8%; HR = 1.080, 95% CI: 0.772-1.512;  = 0.653). In patients hospitalized with HFmrEF, ACEi therapy was associated with reduced 30-month all-cause mortality compared with ARB, whereas the risk of HF-related rehospitalization did not differ.

Background Early detection of respiratory overload is crucial to mechanically ventilated patients, especially during phases of spontaneous breathing. Although a diversity of methods and indices has been established, there is no highly specific approach to predict respiratory failure. This study aimed to evaluate acceleration sensors in abdominal and thoracic wall positions to detect alterations in breathing excursions in a setting of gradual increasing airway resistance. Methods Twenty-nine healthy volunteers were committed to a standardized protocol of a two-minutes step-down spontaneous breathing on a 5 mm, 4 mm and then 3 mm orally placed endotracheal tube. Accelerator sensors in thoracic and abdominal wall position monitored breathing excursions. 15 participants passed the breathing protocol (“completed” group), 14 individuals cancelled the protocol due to subjective intolerance to the increasing airway resistance (“abandoned” group). Results Gradual increased respiratory workload led to a significant decrease of acceleration in abdominal wall position in the “abandoned” group compared to the “completed” group ( p  < 0.001), while these gradual accelerating changes were not observed in thoracic wall position ( p  = 0.484). Thoracic acceleration sensors did not detect any time- and group-specific changes ( p  = 0.746). Conclusions The abdominal wall position of the acceleration sensors may be a non-invasive, economical and practical approach to detect early breathing alterations prior to respiratory failure. Trial registration EK 309–15; by the Ethics Committee of the Faculty of Medicine, RWTH Aachen, Aachen, Germany. Retrospectively registered 28th of December 2015.

Objective This study aims to investigate the prognostic impact of the presence and type of prior hospitalizations in patients with heart failure with mildly reduced ejection fraction (HFmrEF). Background Data investigating the prognostic impact of the present and type of previous all-cause hospitalizations in HFmrEF is limited. Methods Consecutive patients hospitalized with HFmrEF at a single medical center were retrospectively included from 2016 to 2022. The prognosis of patients with a prior hospitalization < 12 months was compared to patients without. The primary endpoint was all-cause mortality at 30 months (median follow-up), the key secondary endpoint was heart failure (HF)-related rehospitalization at 30 months. Results Two thousand one hundred eighty four patients with HFmrEF were included, 34.8% had a previous hospitalization < 12 months (admission to internal medicine and geriatrics: 60.8%, surgical department: 23.5%). The presence of a previous hospitalization was associated with an increased risk of all-cause mortality (38.6% vs. 27.4%; HR = 1.51; 95% CI 1.30–1.76; p  = 0.01) and HF-related rehospitalization at 30 months (21.2% vs. 9.1%; HR = 2.48; 95% CI 1.96–3.14; p  = 0.01), even after multivariable adjustments. However, the department of previous hospitalization (internal medicine vs. surgical) did not significantly affect the risk of 30-months all-cause mortality (37.1% vs. 43.2%; HR = 0.82, 95% CI 0.63–1.08; p  = 0.16) or HF-related rehospitalization (24.0% vs. 16.8%; HR = 1.47, 95% CI 0.98–2.24; p  = 0.07). Finally, the type of previous admission (i.e., elective, emergency vs. HF-related admission) (log-rank p  = 0.29) did not affect the risk of 30-months all-cause mortality. Conclusion Prior hospitalizations within 12 months were independently associated with impaired long-term mortality in patients with HFmrEF, irrespective of the department or type of prior admission.

Decline in mitochondrial function is linked to decreased muscle mass and strength in conditions like sarcopenia and type 2 diabetes. Despite therapeutic opportunities, there is limited and equivocal data regarding molecular cues controlling muscle mitochondrial plasticity. Here we uncovered that the mitochondrial mRNA-stabilizing protein SLIRP, in complex with LRPPRC, is a PGC-1α target that regulates mitochondrial structure, respiration, and mtDNA-encoded-mRNA pools in skeletal muscle. Exercise training effectively counteracts mitochondrial defects caused by genetically-induced LRPPRC/SLIRP loss, despite sustained low mtDNA-encoded-mRNA pools, by increasing mitoribosome translation capacity and mitochondrial quality control. In humans, exercise training robustly increases muscle SLIRP and LRPPRC protein across exercise modalities and sexes, yet less prominently in individuals with type 2 diabetes. SLIRP muscle loss reduces Drosophila lifespan. Our data points to a mechanism of post-transcriptional mitochondrial regulation in muscle via mitochondrial mRNA stabilization, offering insights into how exercise enhances mitoribosome capacity and mitochondrial quality control to alleviate defects. Muscle mass is lost in patients with diabetes, which is associated with mitochondrial disfunction. Here they show that SLIRP maintains muscle mitochondria and that exercise training can compensate for SLIRP loss, improving mitochondrial function and quality control in muscle.