Search

Aims: Patients hospitalized for acute heart failure (HF) could be enrolled in EMPULSE (NCT04157751) upon haemodynamic stabilization and between 24 h and 5 days after hospital admission. The timing of treatment initiation may influence the efficacy and safety of drugs such as empagliflozin. The aim of this study was to evaluate patient characteristics, clinical events, and treatment effects according to time from admission to randomization. Methods and results: The EMPULSE population was dichotomized by median time from hospital admission to randomization (1–2 days vs. 3–5 days). The primary outcome was a hierarchical composite endpoint of time to all‐cause death, number of HF events, time to first HF event, and a ≥5‐point difference in Kansas City Cardiomyopathy Questionnaire total symptom score change from baseline after 90 days, analysed using the win ratio (WR) method. Patients randomized later (3–5 days, average time 3.9 days; n = 312) had a higher risk of experiencing clinical events than patients randomized earlier (1–2 days, average time 1.7 days; n = 215). The treatment effect favoured empagliflozin versus placebo in patients randomized later (3–5 days: WR 1.69, 95% confidence interval [CI] 1.26–2.25) but was attenuated in patients randomized earlier (1–2 days: WR 1.04, 95% CI 0.74–1.44) (interaction p = 0.029). A similar pattern was observed for the composite of HF hospitalization or cardiovascular death and all‐cause hospitalizations (interaction p < 0.1 for both). The reduction of N‐terminal pro‐B‐type natriuretic peptide levels was more pronounced with empagliflozin among patients randomized later than in patients randomized earlier (interaction p = 0.004). Conclusions: Among patients hospitalized for acute HF enrolled in EMPULSE, those randomized later after hospital admission (3–5 days) experienced greater clinical benefit with empagliflozin than those randomized earlier (1–2 days). These findings should be confirmed in future studies before clinical application. [ABSTRACT FROM AUTHOR]

Background: Patients with heart failure with reduced ejection fraction (HFrEF) and central sleep apnea (CSA) are at a very high risk of fatal outcomes. Objective: To test whether the circulating miRNome provides additional information for risk stratification on top of clinical predictors in patients with HFrEF and CSA. Methods: The study included patients with HFrEF and CSA from the SERVE-HF trial. A three-step protocol was applied: microRNA (miRNA) screening (n = 20), technical validation (n = 60), and biological validation (n = 587). The primary outcome was either death from any cause, lifesaving cardiovascular intervention, or unplanned hospitalization for worsening of heart failure, whatever occurred first. MiRNA quantification was performed in plasma samples using miRNA sequencing and RT-qPCR. Results: Circulating miR-133a-3p levels were inversely associated with the primary study outcome. Nonetheless, miR-133a-3p did not improve a previously established clinical prognostic model in terms of discrimination or reclassification. A customized regression tree model constructed using the Classification and Regression Tree (CART) algorithm identified eight patient subphenotypes with specific risk patterns based on clinical and molecular characteristics. MiR-133a-3p entered the regression tree defining the group at the lowest risk; patients with log(NT-proBNP) ≤ 6 pg/mL (miR-133a-3p levels above 1.5 arbitrary units). The overall predictive capacity of suffering the event was highly stable over the follow-up (from 0.735 to 0.767). Conclusions: The combination of clinical information, circulating miRNAs, and decision tree learning allows the identification of specific risk subphenotypes in patients with HFrEF and CSA. [ABSTRACT FROM AUTHOR]

Aims: In patients hospitalized for acute heart failure (AHF) empagliflozin produced greater clinical benefit than placebo. Many patients with AHF are treated with mineralocorticoid receptor antagonists (MRAs). The interplay between empagliflozin and MRAs in AHF is yet to be explored. This study aimed to evaluate the efficacy and safety of empagliflozin versus placebo according to MRA use at baseline in the EMPULSE trial (NCT04157751). Methods and results: In this analysis all comparisons were performed between empagliflozin and placebo, stratified by baseline MRA use. The primary outcome included all‐cause death, heart failure events, and a ≥5 point difference in Kansas City Cardiomyopathy Questionnaire (KCCQ) total symptom score at 90 days, assessed using the win ratio (WR). First heart failure hospitalization or cardiovascular death was a secondary outcome. From the 530 patients randomized, 276 (52%) were receiving MRAs at baseline. MRA users were younger, had lower ejection fraction, better renal function, and higher KCCQ scores. The primary outcome showed benefit of empagliflozin irrespective of baseline MRA use (WR 1.46, 95% confidence interval [CI] 1.08–1.97 and WR 1.27, 95% CI 0.93–1.73 in MRA users and non‐users, respectively; interaction p = 0.52). The effect of empagliflozin on first heart failure hospitalization or cardiovascular death was not modified by MRA use (hazard ratio [HR] 0.58, 95% CI 0.30–1.11 and HR 0.85, 95% CI 0.47–1.52 in MRA users and non‐users, respectively; interaction p = 0.39). Investigator‐reported and severe hyperkalaemia events were infrequent (<6%) irrespective of MRA use. Conclusions: In patients admitted for AHF, initiation of empagliflozin produced clinical benefit and was well tolerated irrespective of background MRA use. These findings support the early use of empagliflozin on top of MRA therapy in patients admitted for AHF. [ABSTRACT FROM AUTHOR]

Aim: Evidence on healthcare resource utilization (HCRU) for hospitalized patients with heart failure (HF) and reduced (HFrEF), mildly reduced (HFmrEF) and preserved (HFpEF) ejection fraction is limited. Methods and results: We analysed HCRU in relation to left ventricular ejection fraction (LVEF) phenotypes, clinical features and in‐hospital and 12‐month outcomes in 16 943 patients hospitalized for HF in a worldwide registry. HFrEF was more prevalent (53%) than HFmrEF (17%) or HFpEF (30%). Patients with HFmrEF and HFpEF were older, more often women, with milder symptoms and more comorbidities, but differences were not pronounced. HCRU was high in all three groups; two or more in‐ and out‐of‐hospital services were required by 51%, 49% and 52% of patients with HFrEF, HFmrEF and HFpEF, respectively, and intensive care unit by 41%, 41% and 37%, respectively. Hospitalization length was similar (median, 8 days). Discharge prescription of neurohormonal inhibitors was <80% for each agent in HFrEF and only slightly lower in HFmrEF and HFpEF (74% and 67%, respectively, for beta‐blockers). Compared to HFrEF, 12‐month all‐cause and cardiovascular mortality were lower for HFmrEF (adjusted hazard ratios 0.78 [95% confidence interval 0.59–0.71] and 0.80 [0.70–0.92]) and HFpEF (0.64 [0.59–0.87] and 0.63 [0.56–0.71]); 12‐month HF hospitalization was also lower for HFpEF and HFmrEF (21% and 20% vs. 25% for HFrEF). In‐hospital mortality, 12‐month non‐cardiovascular mortality and 12‐month all‐cause hospitalization were similar among groups. Conclusions: In patients hospitalized for HF, overall HCRU was similarly high across LVEF spectrum, reflecting the subtle clinical differences among LVEF phenotypes during hospitalization. Discharge prescription of neurohormonal inhibitors was suboptimal in HFrEF and lower but significant in patients with HFpEF and HFmrEF, who had better long‐term cardiovascular outcomes than HFrEF, but similar risk for non‐cardiovascular events. [ABSTRACT FROM AUTHOR]

Aims: The EMPULSE trial evaluated the clinical benefit of empagliflozin versus placebo using the stratified win ratio approach in 530 patients with acute heart failure (HF) after initial stabilization. We aim to elucidate how this method works and what it means, thereby giving guidance for use of the win ratio in future trials. Methods and results: The primary trial outcome is a hierarchical composite of death, number of HF events, time to first HF event, or a ≥5‐point difference in Kansas City Cardiomyopathy Questionnaire (KCCQ) total symptom score change at 90 days. In an overall (unstratified) analysis we show how comparison of all 265 x 265 patients pairs contribute to 'wins' for empagliflozin and placebo at all four levels of the hierarchy, leading to an unstratified win ratio of 1.38 (95% confidence interval [CI] 1.11–1.71; p = 0.0036). How such a win ratio should (and should not) be interpreted is then described. The more complex primary analysis using a stratified win ratio is then presented in detail leading to a very similar overall result. Win ratios for de novo acute HF and decompensated chronic HF patients were 1.29 and 1.39, respectively, their weighted combination yielding an overall stratified win ratio of 1.36 (95% CI 1.09–1.68) (p = 0.0054). Alternative ways of including HF events and KCCQ scores in the clinical hierarchy are presented, leading to recommendations for their use in future trials. Specifically, inclusion of both number of HF events and time‐to‐first HF event appears an unnecessary complication. Also, the use of a 5‐point margin for KCCQ score paired comparisons is not statistically necessary. Conclusions: The EMPULSE trial findings illustrate how deaths, clinical events and patient‐reported outcomes can be integrated into a win ratio analysis strategy that yields clinically meaningful findings of patient benefit. This has implications for future trial designs that recognize the clinical priorities of patient evaluation and the need for efficient progress towards approval of new treatments. [ABSTRACT FROM AUTHOR]

Aim: Acute heart failure can be a life‐threatening medical condition. Delaying administration of intravenous furosemide (time‐to‐diuretics) has been postulated to increase mortality, but prior reports have been inconclusive. We aimed to evaluate the association between time‐to‐diuretics and mortality in the international REPORT‐HF registry. Methods and results: We assessed the association of time‐to‐diuretics within the first 24 h with in‐hospital and 30‐day post‐discharge mortality in 15 078 patients from seven world regions in the REPORT‐HF registry. We further tested for effect modification by baseline mortality risk (ADHERE risk score), left ventricular ejection fraction (LVEF) and region. The median time‐to‐diuretics was 67 (25th–75th percentiles 17–190) min. Women, patients with more signs and symptoms of heart failure, and patients from Eastern Europe or Southeast Asia had shorter time‐to‐diuretics. There was no significant association between time‐to‐diuretics and in‐hospital mortality (p > 0.1). The 30‐day mortality risk increased linearly with longer time‐to‐diuretics (administered between hospital arrival and 8 h post‐hospital arrival) (p = 0.016). This increase was more significant in patients with a higher ADHERE risk score (pinteraction = 0.008), and not modified by LVEF or geographic region (pinteraction > 0.1 for both). Conclusion: In REPORT‐HF, longer time‐to‐diuretics was not associated with higher in‐hospital mortality. However, we did found an association with increased 30‐day mortality, particularly in high‐risk patients, and irrespective of LVEF or geographic region. Clinical Trial Registration: ClinicalTrials.gov Identifier NCT02595814. [ABSTRACT FROM AUTHOR]

Aims: Recovery of well‐being after hospitalisation for acute heart failure (AHF) is a measure of the success of interventions and the quality of care but has rarely been quantified. Accordingly, we measured health status after discharge in an international registry (REPORT‐HF) of AHF. Methods and results: The analysis included 4606 patients with AHF who survived to hospital discharge, had known vital status at 6 months, and were enrolled in the United States of America, Russian Federation, or Western Europe, where the Kansas City Cardiomyopathy Questionnaire (KCCQ) was administered. Median age was 69 years (quartiles 59–78), 40% were women, and 34% had a left ventricular ejection fraction (LVEF) <40%, and 12% patients died by 6 months. Of 2475 patients with a follow‐up KCCQ, 28% were 'alive and well' (KCCQ >75), while 43% had poor health status (KCCQ ≤50). Being 'alive and well' was associated with new‐onset AHF, LVEF <40%, younger age, higher baseline KCCQ, country, and race. Associations were similar for increasing health status, with the exception of country and addition of comorbidities. Conclusion: In this international global registry, health status recovery after AHF hospitalisation was highly variable. Those with the best health status at 6 months were younger, had new‐onset heart failure, and higher baseline KCCQ; nearly one‐third of survivors were 'alive and well'. Investigating reasons for changes in KCCQ after hospitalisation might identify new therapeutic targets to improve patient‐centred outcomes. [ABSTRACT FROM AUTHOR]

Aims: Few prior studies have investigated differences in precipitants leading to hospitalizations for acute heart failure (AHF) in a cohort with global representation. Methods and results: We analysed the prevalence of precipitants and their association with outcomes in 18 553 patients hospitalized for AHF in REPORT‐HF (prospective international REgistry to assess medical Practice with lOngitudinal obseRvation for Treatment of Heart Failure) according to left ventricular ejection fraction subtype (reduced [HFrEF] and preserved ejection fraction [HFpEF]) and presentation (new‐onset vs. decompensated chronic heart failure [DCHF]). Patients were enrolled from 358 centres in 44 countries stratified according to Latin America, North America, Western Europe, Eastern Europe, Eastern Mediterranean and Africa, Southeast Asia, and Western Pacific. Precipitants were pre‐with mutually exclusive categories and selected according to the local investigator's discretion. Outcomes included in‐hospital and 1‐year mortality. The median age was 67 (interquartile range 57–77) years, and 39% were women. Acute coronary syndrome (ACS) was the most common precipitant in patients with new‐onset heart failure in all regions except for North America and Western Europe, where uncontrolled hypertension and arrhythmia, respectively, were the most common precipitants, independent of confounders. In patients with DCHF, non‐adherence to diet/medication was the most common precipitant regardless of region. Uncontrolled hypertension was a more likely precipitant in HFpEF, non‐adherence to diet/medication, and ACS were more likely precipitants in HFrEF. Patients admitted due to worsening renal function had the worst in‐hospital (5%) and 1‐year post‐discharge (30%) mortality rates, regardless of region, heart failure subtype and admission type (pinteraction >0.05 for all). Conclusion: Data on global differences in precipitants for AHF highlight potential regional differences in targets for preventing hospitalization for AHF and identifying those at highest risk for early mortality. [ABSTRACT FROM AUTHOR]

Aims: Whereas guidelines recommend the routine use of natriuretic peptides (NPs) in heart failure (HF) care, the clinical relevance and prognostic potential of midregional pro-adrenomedullin (MR-proADM) is less well established. We aimed to compare the prognostic potential of MR-proADM after acute decompensation for systolic HF with that of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and midregional pro-atrial NP (MR-proANP), to investigate the significance of high/rising MR-proADM, and to evaluate the incremental prognostic yield of repeat measurements.Methods and Results: The Interdisciplinary Network Heart Failure (INH) programme enrolled patients hospitalized for acute systolic HF and followed them for 18 months (100% complete). Of 1022 INH participants, 917 (68 ± 12 years, 28% female) who had biomaterials available were enrolled. High MR-proADM was associated with more impaired left ventricular function, higher comorbidity burden, lower doses of HF medications, and lower likelihood of left ventricular reverse remodelling. Compared with NPs, MR-proADM had superior prognostic significance (concordance index 0.72 for all-cause mortality), improved Cox regression models including NPs (P < 0.001), and was the only biomarker also predicting non-cardiac death (hazard ratio 1.8 vs. 1.0). In the setting of low NPs, patients with high MR-proADM experienced non-cardiac death more often. Six month MR-proADM enhanced models including baseline MR-proADM (P < 0.001) for prediction of all-cause death (net reclassification index: 0.48, 95% confidence interval 0.19-0.78).Conclusion: MR-proADM was found to correlate with the global disease burden in HF and proved a potent prognostic indicator, capturing the risk for both cardiac and non-cardiac death. Serial MR-proADM measurements further enhanced risk assessment, thus facilitating substantial reclassification. [ABSTRACT FROM AUTHOR]

Background This study investigated the correlation of levels of and changes in serial high-sensitivity cardiac troponin I (hsTnI) with subsequent clinical event rates and changes in cardiac morphology and function in patients hospitalized for acutely decompensated heart failure (ADHF). Methods and results HsTnI levels were determined in 875 ADHF patients before discharge from hospital (baseline cohort) and clinical outcomes assessed after 180 days. HsTnI was re-measured at 180 days in 456/875 patients (follow-up cohort). Follow-up hsTnI values were grouped according to baseline hsTnI tertiles; echocardiographic changes from 0–180 days and event rates from 180–540 days were assessed in these subgroups. At baseline and 180-day follow-up, hsTnI levels were elevated (> 0.06 ng/mL) in 322/875 (37%) and 68/456 (15%) patients, respectively. At 180 days, 85/875 patients (9.7%) had died (cardiovascular causes: 56/875 [6.4%]). Hazard ratios (HR) and 95% confidence intervals (CI) for all-cause and cardiovascular mortality (per two-fold hsTnI increase) were 1.2 (1.0–1.3; p = 0.004) and 1.2 (1.1–1.4; p = 0.001), respectively. In the follow-up cohort, 35/456 patients (7.7%) died between days 180 and 540 (cardiovascular death: 20/456, 4.4%). HsTnI was a significant predictor of cardiovascular re-hospitalization within 180–540 days (HR 1.2, 95% CI 1.0–1.4; p = 0.028). Patients with hsTnI in the lowest tertile at follow-up had more frequent and more pronounced reverse cardiac remodelling on echocardiography. Conclusions Elevated baseline hsTnI was common and associated with adverse clinical outcomes. Changes in hsTnI from baseline to 180-day follow-up predicted longer-term risk. Low or decreasing hsTnI was associated with better reverse cardiac remodelling and more favourable long-term outcomes. Clinical Trial Registration URL http://www.controlled-trials.com . Unique identifier: ISRCTN23325295. [ABSTRACT FROM AUTHOR]

Aim This study investigates the prevalence and prognostic impact of central and small airways obstruction (CAO and SAO) in patients with stable heart failure (HF). Methods & results Spirometry was performed in 585 outpatients (mean age 65 ± 12 years, 75% male) six months after hospitalisation for acute decompensation secondary to HF with ejection fraction < 40%. We assessed forced expiratory volume in the first second (FEV1), forced vital capacity (FVC) and mid-expiratory flow (MEF) at 50% of FVC. CAO was defined by FEV1/FVC < 0.7. SAO was defined by FEV1/FVC ≥ 0.7 plus MEF < 60% of predicted value. CAO and SAO were excluded in 359 patients (61% of all). MEF < 60% predicted was found in 226 patients (39% of all), among those 88 with CAO (15% of all) and 138 (24% of all) with SAO. During a twelve month follow-up, 42 patients (7.2%) died. Mortality rates of patients with CAO and SAO were comparable (12.5% and 10.9%, respectively, p = 0.74), and both higher than in patients without airways obstruction (4.5%, both p < 0.01). In univariable Cox regression analysis, both CAO and SAO were associated with 2-fold increased all-cause mortality risk (hazard ratios [95% confidence intervals]: 2.78 [1.33–6.19], p = 0.007 and 2.51 [1.24–5.08], p = 0.010, respectively). Adjustment for determinants of CAO and SAO, prognostic markers of heart failure and comorbidities attenuated the association of mortality with CAO but not with SAO. Conclusions SAO is more common than CAO and indicates an increased mortality risk in HF. Thus, reduced MEF may be a feature of patients at risk and merits special attention in HF management. [ABSTRACT FROM AUTHOR]

Aims Serum cortisol independently predicts mortality risk in patients with systolic heart failure. Salivary cortisol may provide advantages as it better reflects the biologically active free compound. Furthermore, sampling is non-invasive and may easily be performed in outpatients. We comparatively evaluated associations of morning (MSC) vs. evening salivary cortisol (ESC) and all-cause mortality risk. Methods and results MSC (8 am) and ESC (9 pm) were determined in 229 patients with heart failure participating in the Interdisciplinary Network for Heart Failure program (66 ± 13 years; 21% female; 37% New York Heart Association (NYHA) class III/IV, median left ventricular ejection fraction 33%). The association of cortisol with mortality risk was determined by univariate and Cox multivariable regression analyses adjusting for age, sex, NYHA class, and N-terminal pro-hormone B-type natriuretic peptide. Compared to ESC, MSC was significantly higher and exhibited a higher variance: median 0.59 ng/ml (interquartile range 0.41–0.93) vs. 0.25 ng/ml (0.15–0.48), p < 0.001. During 18 months of follow-up, 25 (11%) patients died. In univariate and multivariable models mortality risk was not increased in the highest MSC quartile: crude hazard ratio (HR) 1.81 (95% confidence interval 0.79–4.14, p = 0.160), adjusted HR 1.26 (0.51–3.13, p = 0.616). However, patients in the highest ESC quartile had a significantly increased mortality risk, suggesting that associations of high ESC and increased mortality were independent of disease severity: crude HR 3.33 (1.50–7.42, p = 0.003), adjusted HR 2.49 (1.01–6.14, p = 0.047). ESC alone proved the best predictor of mortality. Conclusion High ESC but not MSC levels independently predict increased mortality risk in heart failure. [ABSTRACT FROM AUTHOR]

Objective The prognostic potential of depressive symptoms independent of somatic features of heart failure severity has repeatedly been demonstrated. However, patient-reported functional status has rarely been accounted for in these studies. Thus, it has remained unclear to what extent the predictive power of depressive symptoms may mirror functional status. We therefore aimed to evaluate the prognostic value of depressive symptoms adjusting for patient-reported functional status in a large, well-characterized sample of patients with systolic heart failure. Methods Eight hundred sixty-three patients, 67 ± 12 years old, 72% men, and 42% with New York Heart Association functional classes III/IV, who participated in the extended Interdisciplinary Network Heart Failure (INH) study were investigated. We assessed depressive symptoms using the Patient Health Questionnaire (PHQ-9) and patient-reported functional status with the Kansas City Cardiomyopathy Questionnaire (KCCQ). Data on survival was obtained after a follow-up of 18 months (100% complete). Results Depressive symptoms predicted mortality risk (HR per PHQ-9 scale point = 1.07, 95% CI 1.04–1.09, p < .001), even after adjustment for heart failure severity and co-morbidities (HR = 1.04, 95% CI 1.01–1.07, p = .017). However, they were no longer significant predictors (HR = 1.01, 95% CI 0.98–1.05, p = 0.46) after additional adjustment for patient-reported functional status, which proved predictive of mortality risk (HR = 0.90, 95% CI 0.82–0.99, p = .025). Conclusion Our results suggest that the association of depressive symptoms with functional status may at least partly explain the prognostic potential of depressive symptoms. [ABSTRACT FROM AUTHOR]

Abstract: Background: The diagnosis of chronic obstructive pulmonary disease (COPD) in patients with systolic heart failure (SHF) is challenging because symptoms of both conditions overlap. We aimed to estimate the prevalence, correlates and prognostic impact of true COPD in patients with SHF. Methods: To diagnose COPD under stable conditions according to the guidelines, pulmonary function testing (PFT) was performed in 619 patients six months after hospitalization for congestive SHF. In 272 patients, PFT had been also performed prior to discharge. Results: In the total cohort, COPD was reported in 23% (144/619). PFT under stable conditions revealed that COPD was absent in 73% (449/619), unconfirmed in 18% (112/619), and proven in 9% (58/619). In 272 patients with serial PFT, initial airway obstruction was found in 19% (51/272) but had resolved in 47% of those (24/51) after six months. Initial hyperinflation detected by bodyplethysmography strongly predicted proven COPD six months later: odds ratio for elevated intrathoracic gas volume 12.8, 95% confidence interval (CI) 2.5–65.9; p=0.002. After a median follow-up of 34months, 27% of the total cohort (165/619) had died. Only proven COPD was associated with an increased mortality risk after adjustment for age, sex, NYHA functional class, ejection fraction, atrial fibrillation, smoking, renal dysfunction and diabetes: hazard ratio 1.64, 95%CI 1.03–2.63; p=0.039. Conclusions: Airway obstruction is a dynamic phenomenon in SHF. Therefore, a valid diagnosis of COPD in SHF demands serial PFT under stable conditions with special attention to hyperinflation. COPD proven by PFT is associated with an increased all-cause mortality risk. [Copyright &y& Elsevier]

Abstract: Background: Therapeutic and prognostic implications of subclinical thyroid dysfunction in patients with heart failure (HF) are unclear. We compared the prognostic impact of euthyroidism, subclinical thyroid dysfunction, and euthyroid sick syndrome (ESS) in systolic HF. Methods: We included 1032 patients hospitalized for systolic HF (left ventricular ejection fraction [LVEF] ≤40%) who participated in a randomized trial assessing the effects of a HF disease management program. Patients with incomplete thyroid function tests or thyrotropic medication were excluded. In the remaining 758 subjects, the risk of all-cause death was estimated based on TSH only, or full thyroid function profile. Changes of thyroid function after six months were assessed in 451 subjects. Results: Subclinical thyroid dysfunction was present in 103 patients at baseline (14%). No differences were found between groups regarding NYHA class (P=0.29), and LVEF (P=0.60). After a median follow-up of three years patients with ESS (n=13) had a 3-fold age-adjusted increased risk of death compared to euthyroid patients (P=0.001). However, neither subclinical hyperthyroidism (HR 1.18, 95%CI:0.82–1.70) nor hypothyroidism (HR 1.07, 95%CI:0.58–1.98) were associated with increased age-adjusted mortality risk. Subclinical thyroid dysfunction had normalized spontaneously at follow-up in 77% of patients. However, persistent subclinical thyroid dysfunction was also not associated with worse outcome. Conclusions: In this large well-characterized HF cohort, subclinical thyroid dysfunction did not predict an increased mortality risk. Thus, in patients with moderate to severe HF, further diagnostic and therapeutic procedures for subclinical thyroid dysfunction appear dispensable. ESS was an infrequent but important indicator of a poor prognosis in HF. Clinical trial registration: URL: http://www.controlled-trials.com. Unique identifier: ISRCTN23325295. [Copyright &y& Elsevier]

Abstract: Aims: Depression is common in heart failure (HF) and associated with adverse outcomes. This study aimed to investigate incidence rates and predictors of depression in patients sampled from four subprojects of the German Competence Network Heart Failure. Methods: Eight hundred thirty nine symptomatic HF patients free of depression at baseline underwent repeat depression screening (Patient Health Questionnaire, PHQ-9) after 12months. Ordered logistic regression analysis was employed to search for predictors of incident depression. Results: Incident minor (major) depression was observed in 61 (7.3%) and 47 (5.6%) of the population. Depression was recurrent in 15 (25%) and 16 (34%), respectively. Multiple regression analysis revealed seven variables predicting minor or major depression: Previous depressive episode (odds ratio [OR] 4.04, 95% confidence interval [CI] 2.37–6.89, p ≤0.001), previous resuscitation (OR 2.44, CI 1.23–4.81, p =0.010), current smoking (OR 2.06, CI 1.08–3.50, p =0.008), >4 visits/year to general practitioner (OR 1.67, CI 1.06–2.63, p =0.026), New York Heart Association class (OR 1.54/class, 95% CI 1.05–2.25, p =0.027), PHQ-9 baseline sum-score (OR 1.18/point, CI 1.11–1.27, p <0.001), and SF-36 physical functioning (OR 1.08/−5 points, CI 1.03–1.13, p =0.002). Conclusions: In these HF patients initially free of depression annual incidence rates were high. Several independent predictors allowed identification of patients at particular risk. Although obtained in a selected cohort these findings call, in view of the grave prognosis of HF patients with comorbid depression, for regular depression screening and development of specific supportive strategies to improve patient care and outcomes in HF. [Copyright &y& Elsevier]

Abstract: Background: Depression is highly prevalent in patients with chronic heart failure (CHF) and may bias patients'' reports of their health-related quality of life (HRQoL). Depressed patients may rate their limitations of HRQoL worse even when their condition is rather good. We aimed to examine whether co-morbid depression alters the relationship between disease severity and HRQoL, thus compromising the validity of a CHF-specific HRQoL measure. Methods: A sample of 233 outpatients with CHF (mean age 64.5 years, 70% male) was evaluated. Depression was measured with the Patient Health Questionnaire and CHF-specific HRQoL with the Kansas City Cardiomyopathy Questionnaire (KCCQ). CHF severity was assessed with physician ratings of the New York Heart Association (NYHA) functional class. Results: Both NYHA functional class and depression independently impacted the various subscales of the KCCQ. Regarding the symptom- and function-related subscales, a dose–response relationship between disease severity and HRQoL was observed also in depressed patients. In contrast, in the quality of life subscale covering life satisfaction an interaction effect of disease severity and depression was found. In this subscale, a dose–response relationship between increasing disease severity and worsening HRQoL was no longer present among the depressed. Conclusions: Both disease severity and depression impacted each heart failure-specific HRQoL dimension while the presence of depression seemed to distort the relationship between disease severity and HRQoL in the quality of life subscale. As quality of life may depend more on the presence of depression than on the severity of CHF, assessing depression may help interpreting HRQoL scores. [Copyright &y& Elsevier]

Objectives: This study sought to develop a rapid method for the detection of activating autoantibodies directed against the β1-adrenoceptor (anti-β1-Abs) in patients with heart failure. Background: The anti-β1-Abs are supposed to play a pathophysiological role in heart failure. However, there is no reliable method for their detection. With a complex screening strategy (enzyme-linked immunosorbent assay, immunofluorescence, cyclic adenosine monophosphate [cAMP]–radioimmunoassay) we have previously identified antibodies targeting the second extracellular β1-receptor loop (anti-β1-ECII) in 13% of patients with ischemic cardiomyopathy (ICM) and in 26% with dilated cardiomyopathy (DCM). Methods: To detect anti-β1-Abs, we measured β1-receptor–mediated increases in intracellular cAMP by fluorescence resonance energy transfer using a highly sensitive cAMP sensor (Epac1-based fluorescent cAMP sensor). Results: The immunoglobulin G (IgG) prepared from 77 previously antibody-typed patients (22 ICM/55 DCM) and 50 matched control patients was analyzed. The IgG from all 22 previously anti-β1-ECII–positive patients (5 ICM/17 DCM) induced a marked cAMP increase, indicating receptor activation (49.8 ± 4.2% of maximal isoproterenol-induced signal). The IgG from control patients and 32 previously anti-β1-ECII–negative patients (17 ICM/15 DCM) did not significantly affect cAMP. Surprisingly, our technology detected anti-β1-Abs in 23 DCM patients formerly judged antibody-negative, but their cAMP signals were generally lower (31.3 ± 6.8%) than in the previous group. “Low”-activator anti-β1-Abs were blocked preferentially by peptides corresponding to the first, and “high”-activator anti-β1-Abs by peptides corresponding to the second β1-extracellular loop. Beta-blockers alone failed to fully prevent anti-β1-ECII–induced receptor activation, which could be achieved, however, by the addition of β1-ECII peptides. Conclusions: Our novel method of detecting anti-β1-Abs proved to be fast and highly sensitive. It also revealed an insufficient ability of beta-blockers to prevent anti-β1-ECII–induced receptor activation, which opens new venues for the research on anti-β1-Abs and eventual treatment options in heart failure. [Copyright &y& Elsevier]

Today,dilated cardiomyopathy (DCM)represents the main cause of severe heart failure and disability in younger adults and thus is a challenge for public health.About 30%of DCM cases are genetic in ori - gin;however,the large majority of cases are sporadic,and a viral or immune pathogenesis is suspected. Following the established postulates for pathogenesis of autoimmune diseases,here we provide direct evidence that an autoimmune attack directed against the cardiac β1-adrenergic receptor may play a causal role in DCM.First,we immunized inbred rats against the second extracellular β1-receptor loop (β1-ECII; 100%sequence identity between human and rat)every month.All these rats developed f irst,receptor- stimulating anti --β1-ECII Ab's and then,after 9 months,progressive severe left ventricular dilatation and dysfunction.Second,we transferred sera from anti --β 1-ECII --positive and Ab-negative animals every month to healthy rats of the same strain.Strikingly,all anti --β1-ECII --transferred rats also developed a similar cardiomyopathic phenotype within a similar time frame,underlining the pathogenic potential of these receptor Ab's.As a consequence,β 1-adrenergic receptor --targeted autoimmune DCM should now be categorized with other known receptor Ab-mediated autoimmune diseases,such as Graves disease or myasthenia gravis.Although carried out in an experimental animal model,our findings should fur- ther encourage the development of therapeutic strategies that combat harmful anti--β 1-ECII in receptor Ab--positive DCM patients. [ABSTRACT FROM AUTHOR]

Background: Chronic heart failure (CHF) is a major cause of morbidity and mortality worldwide, placing a significant burden on health care systems. The concept of telemedicine for CHF was first introduced in the late 1990s, and since 2010, studies have demonstrated its potential to improve patient outcomes and reduce health care costs. Over the following decade, technological advancements and changes in health care policy led to the development of more sophisticated telemedicine solutions for CHF, including remote patient management through invasive or noninvasive telemonitoring devices, mobile apps, and virtual consultations. Years of public funding in Germany have generated evidence that remote patient management improves outcomes for patients with CHF, such as quality of life, and reduces hospital admissions. Based on these data, the Federal Joint Committee (Gemeinsamer Bundesausschuss; G-BA) decided, independently of the current European Society of Cardiology recommendations, to incorporate telemedicine as a standard digital intervention for high-risk patients with reduced left ventricular ejection fraction in Germany in 2020., Objective: This review aims to illustrate the journey from the initial concept through pioneering studies that led to telemedicine's integration into standard care, and to share current experiences that have positioned Germany as a leader in cardiovascular telemedicine., Methods: We review and discuss existing literature and evidence on the development and implementation of telemonitoring for CHF in Germany over the past 20 years. Relevant studies, reports, and guidelines were identified through a comprehensive search of electronic databases, including PubMed, Google Scholar, and specialized journals focused on CHF telemonitoring., Results: Pioneering studies, such as the TIM-HF2 (Telemedical Interventional Management in Heart Failure II) and IN-TIME (Influence of Home Monitoring on Mortality and Morbidity in Heart Failure Patients with Impaired Left Ventricular Function) trials, demonstrated the effectiveness of remote patient management applications for patients with CHF in Germany and their applicability to current practices involving both invasive and noninvasive methods. Collaborations between researchers and technology developers overcame barriers, leading to sustainable improvements in patient care. Ongoing research on artificial intelligence applications for prioritizing and interpreting individual health data will continue to transform digital health care., Conclusions: The establishment of telemedical care for patients with HF across Europe is likely to benefit from experiences in Germany, where significant improvements have been achieved in the care of patients with HF., (©Sebastian Spethmann, Gerhard Hindricks, Kerstin Koehler, Stefan Stoerk, Christiane E Angermann, Michael Böhm, Birgit Assmus, Sebastian Winkler, Martin Möckel, Mirja Mittermaier, Monika Lelgemann, Daniel Reuter, Ralph Bosch, Alexander Albrecht, Stephan von Haehling, Thomas M Helms, Stefan Sack, Tarek Bekfani, Jan Wolfgang Gröschel, Magdalena Koehler, Christoph Melzer, Jan Wintrich, Bettina Zippel-Schultz, Georg Ertl, Claus Vogelmeier, Nikolaos Dagres, Jasmin Zernikow, Friedrich Koehler. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 04.12.2024.)

Background: Outcomes of hospitalized patients with heart failure (HF) and characteristics of advanced HF stage may vary across left ventricular ejection fraction (LVEF) and world regions., Objectives: This study sought to analyze characteristics of hospitalized advanced HF patients across LVEF spectrum, world regions, and country income., Methods: Among 18,553 hospitalized patients with acute HF (7,902 new-onset HF and 10,651 decompensated chronic HF) enrolled in the global registry REPORT-HF (International Registry to Assess Medical Practice With Longitudinal Observation for Treatment of Heart Failure), we analyzed characteristics and outcomes of patients with advanced HF, defined as previously diagnosed HF; severe symptoms before current admission (NYHA functional class III/IV); and ≥1 HF-related hospitalization in the preceding 12 months, excluding the current. Differences among hospitalized advanced HF subgroups stratified by LVEF, world region, and country income were examined., Results: Among 6,999 patients with decompensated chronic HF and available previous NYHA functional class and HF hospitalization status, 3,397 (48.5%; 18.3% of the total population) had advanced HF. Of these, 44.5% had severely reduced (≤30%), 34.9% mildly/moderately reduced (31%-49%), and 20.7% preserved (≥50%) LVEF. Patients from Eastern Europe had the lowest 1-year mortality (23%), whereas those from Southeast Asia had the highest (37%). Patients from lower-middle-income countries were younger, with shorter HF duration and lower comorbidity prevalence, received fewer beta-blockers and HF-devices, and had higher 1-year mortality (34%) than upper-middle- (26%) or high-income countries (27%; P = 0.018). Adjusted 1-year mortality risk did not differ among LVEF subgroups (all P > 0.05), nor did 1-year HF hospitalization rate (P = 0.56)., Conclusions: Hospitalized patients with advanced HF and preserved LVEF had similarly adverse outcomes as those with reduced LVEF. Patients from lower-middle-income countries had less implementation of HF therapies and higher 1-year mortality., Competing Interests: Funding Support and Author Disclosures Novartis Pharma AG sponsored REPORT-HF. The Steering Committee was responsible for the trial design and supervised patient recruitment and clinical management of the trial. Novartis Pharma AG oversaw data collection and management. The Steering Committee oversaw the analysis and interpretation of the data; preparation, review, and approval of the manuscript; and the decision to submit the manuscript for publication. The corresponding author had full access to all the data of the study and had final responsibility for the decision for manuscript submission. Dr Bistola has received honoraria for lectures or Advisory Boards from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Pfizer, and Roche Diagnostics. Dr Farmakis has received lecture honoraria, consulting or Advisory Board fees and/or grants from AstraZeneca, Bayer, Boehringer Ingelheim, Leo, Myocardial Solutions, Novartis, Remedica, Roche Diagnostics, and Viatris, all outside the present work. Dr Tromp is supported by the National University of Singapore Start-up grant, the tier 1 grant from the Ministry of Education, and the Clinician Scientist–Individual Research Grant New Investigator Grant from the National Medical Research Council; has received research support from AstraZeneca and consulting or speaker fees from Daiichi-Sankyo, Boehringer Ingelheim, Roche Diagnostics and Us2.ai; and owns patent US-10702247-B2 unrelated to the present work. Dr Angermann has been a member of the Executive Committee of International Registry to Assess Medical Practice With Longitudinal Observation for Treatment of Heart Failure (REPORT-HF) and has received speaker honoraria, personal fees, and publication support from Novartis in the context of REPORT-HF; has received grant support from the German Ministry for Education and Research (grants 01GI0205 and 01GI1202A); and grant support, personal fees, and/or nonfinancial support from Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly Company, Medtronic, Novo Nordisk, ResMed, Thermo Fisher, and Vifor, all outside of the submitted work. Dr Dahlström has received research grants from Pfizer, AstraZeneca, Vifor Pharma, Boehringer Ingelheim, Boston Scientific, and Roche Diagnostics and honoraria/consultancies from AstraZeneca, Pfizer, and Amgen, all outside the submitted work. Dr Ghadanfar is a former employee of Novartis Pharma AG and owns Novartis shares. Dr Schweizer is an employee of Novartis Pharma AG and owns Novartis shares. Dr Collins has received research support from the National Institutes of Health, Patient-Centered Outcomes Research Institute, U.S. Department of Defense, and Beckman Coulter and consulting fees from Abbott, Redesign Health, and Reprieve Cardiovascular, Inc. Dr Lam has been supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Novo Nordisk and Roche Diagnostics; has served as consultant or on the Advisory Board/Steering Committee/Executive Committee for Alleviant Medical, Allysta Pharma, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CardioRenal, Cytokinetics, Darma Inc, EchoNous Inc, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Quidel Corporation, Radcliffe Group Ltd, Recardio Inc, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics, and Us2.ai; and serves as cofounder and nonexecutive director of Us2.ai. Dr Filippatos has received lecture fees and/or Advisory and/or Trial Committee membership from Bayer, Boehringer Ingelheim, Servier, Novartis, Impulse Dynamics, Vifor, Medtronic, Cardior, and Novo Nordisk and research grants from the European Union. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aim: To assess the level of self-efficacy in patients with heart failure (HF), and identify differences between important subgroups including sex, and to identify the determinants of high self-efficacy., Methods and Results: This was a pooled cross-sectional analysis of 2,030 patients from four prospective studies conducted within the German Competence Network Heart Failure. We used the Self-efficacy Subscale and the Overall Summary Score (OSS) of the Kansas City Cardiomyopathy Questionnaire (KCCQ-23) to assess self-efficacy and health-related quality of life. The cut-off of 75 score points was used for the dichotomization into high (≥75) vs low (<75) self-efficacy. Depressive symptoms were measured by the Patient Health Questionnaire (PHQ-9). A total of 1,615 patients with HF provided complete self-efficacy scores: mean age 66.6±12.3 years, 431 (27%) women. Mean self-efficacy was 67.5±24.9, with 907 patients (56.2%) showing high self-efficacy and 708 patients (43.8%) showing low self-efficacy. Men had higher self-efficacy scores than women (68.7±24.5 vs. 64.2±26.0; p=0.001). Multivariable logistic regression identified KCCQ-OSS (OR per 5-point increase 1.08, 95%CI 1.04-1.12), female sex (OR 0.72, 95%CI 0.56-0.94), depressive symptoms (OR per 3-point increase in PHQ-9 0.90, 95%CI 0.83-0.98), and acute HF (0.46, 95% CI 0.34-0.62) as important predictors of high self-efficacy., Conclusion: In patients with HF, women seemed to exhibit lower self-efficacy than men. Health-related quality of life and psychological well-being were dominant determinants of self-efficacy. Future studies should investigate the role of self-efficacy as a therapeutic target for tailored and sex-specific nursing interventions., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Aim: The EMPULSE (EMPagliflozin in patients hospitalised with acUte heart faiLure who have been StabilizEd) trial showed that, compared to placebo, the sodium-glucose cotransporter 2 inhibitor empagliflozin (10 mg/day) improved clinical outcomes of patients hospitalized for acute heart failure (HF). We investigated whether efficacy and safety of empagliflozin were consistent across the spectrum of left ventricular ejection fraction (LVEF)., Methods and Results: A total of 530 patients hospitalized for acute de novo or decompensated HF were included irrespective of LVEF. For the present analysis, patients were classified as HF with reduced (HFrEF, LVEF ≤40%), mildly reduced (HFmrEF, LVEF 41-49%) or preserved (HFpEF, LVEF ≥50%) ejection fraction at baseline. The primary endpoint was a hierarchical outcome of death, worsening HF events (HFE) and quality of life over 90 days, assessed by the win ratio. Secondary endpoints included individual components of the primary endpoint and safety. Out of 523 patients with baseline data, 354 (67.7%) had HFrEF, 54 (10.3%) had HFmrEF and 115 (22.0%) had HFpEF. The clinical benefit (hierarchical composite of all-cause death, HFE and Kansas City Cardiomyopathy Questionnaire total symptom score) of empagliflozin at 90 days compared to placebo was consistent across LVEF categories (≤40%: win ratio 1.35 [95% confidence interval 1.04, 1.75]; 41-49%: win ratio 1.25 [0.66, 2.37)] and ≥50%: win ratio 1.40 [0.87, 2.23], p interaction  = 0.96) with a favourable safety profile. Results were consistent across individual components of the hierarchical primary endpoint., Conclusion: The clinical benefit of empagliflozin proved consistent across LVEF categories in the EMPULSE trial. These results support early in-hospital initiation of empagliflozin regardless of LVEF., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Multimorbidity (two or more comorbidities) is common among patients with acute heart failure, but comprehensive global information on its prevalence and clinical consequences across different world regions and income levels is scarce. This study aimed to investigate the prevalence of multimorbidity and its effect on pharmacotherapy and prognosis in participants of the REPORT-HF study., Methods: REPORT-HF was a prospective, multicentre, global cohort study that enrolled adults (aged ≥18 years) admitted to hospital with a primary diagnosis of acute heart failure from 358 hospitals in 44 countries on six continents. Patients who currently or recently participated in a clinical treatment trial were excluded. Follow-up data were collected at 1-year post-discharge. The primary outcome was 1-year post-discharge mortality. All patients in the REPORT-HF cohort with full data on comorbidities were eligible for the present study. We stratified patients according to the number of comorbidities, and countries by world region and country income level. We used one-way ANOVA, χ 2 test, or Mann-Whitney U test for comparisons between groups, as applicable, and Cox regression to analyse the association between multimorbidity and 1-year mortality., Findings: Between July 23, 2014, and March 24, 2017, 18 553 patients were included in the REPORT-HF study. Of these, 18 528 patients had full data on comorbidities, of whom 11 360 (61%) were men and 7168 (39%) were women. Prevalence rates of multimorbidity were lowest in southeast Asia (72%) and highest in North America (92%). Fewer patients from lower-middle-income countries had multimorbidity than patients from high-income countries (73% vs 85%, p<0·0001). With increasing comorbidity burden, patients received fewer guideline-directed heart failure medications, yet more drugs potentially causing or worsening heart failure. Having more comorbidities was associated with worse outcomes: 1-year mortality increased from 13% (no comorbidities) to 26% (five or more comorbidities). This finding was independent of common baseline risk factors, including age and sex. The population-attributable fraction of multimorbidity for mortality was higher in high-income countries than in upper-middle-income or lower-middle-income countries (for patients with five or more comorbidities: 61% vs 27% and 31%, respectively)., Interpretation: Multimorbidity is highly prevalent among patients with acute heart failure across world regions, especially in high-income countries, and is associated with higher mortality, less prescription of guideline-directed heart failure pharmacotherapy, and increased use of potentially harmful medications., Funding: Novartis Pharma., Translations: For the Arabic, French, German, Hindi, Mandarin, Russian and Spanish translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests JGFC reports grants and personal fees from Amgen, Bayer, Bristol Myers Squibb, and Torrent Pharmaceuticals; personal fees from AstraZeneca, Myokardia, Servier, and Abbott; grants, personal fees, and non-financial support from Medtronic, Novartis, and Vifor; and grants and non-financial support from Pharmacosmos and PharmaNord. UD reports research support from AstraZeneca, Pfizer, Boehringer Ingelheim, Vifor, Roche Diagnostics, and Boston Scientific; and speaker's honoraria and consultancies from AstraZeneca, Novartis, and Amgen. GE reports personal fees from AstraZeneca, Abbott, Boehringer Ingelheim, Novartis, and Vifor, all outside the submitted work; non-financial support from the University Hospital Würzburg, and the Comprehensive Heart Failure Center Würzburg; and grant support from German Ministry for Education and Research (BMBF). SVP reports support from Novartis for the present manuscript; consulting fees from Abbott and Bago; and personal fees from Abbott, Boehringer Ingelheim, and Bago. MG and AO were formerly Novartis employees. AS is employed by Novartis. SPC reports research grants from the National Institutes of Health, Agency for Research and Quality, American Heart Association, and the Patient-Centered Outcomes Research Institute; and consulting fees from Novartis, Medtronic, Aiphia, Boehringer Ingelheim, Siemens, and Ortho Clinical. GF reports research grants from the EU; committee fees from Novartis related to REPORT-HF; and lecture fees or being a committee member in trials or registries sponsored by Servier, Boehringer Ingelheim, Medtronic, Vifor, Amgen, and Bayer. CSPL is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Bayer and Roche Diagnostics; has served as consultant or on the Advisory Board, Steering Committee, or Executive Committee for Actelion, Alleviant Medical, Allysta Pharma, Amgen, AnaCardio, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Darma, EchoNous, Eli Lilly, Impulse Dynamics, Ionis Pharmaceutical, Janssen Research & Development, Medscape WebMD Global, Merck, Novartis, Novo Nordisk, Prosciento, Radcliffe Group, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics, and Us2.ai; and serves as co-founder and non-executive director of Us2.ai. JT has received consulting or speaker fees from Daiichi-Sankyo, Boehringer Ingelheim, Roche Diagnostics, and Us2.ai; and owns patent US-10702247-B2 unrelated to the present work. CEA reports grant support, personal fees, or non-financial support from Abbott, AstraZeneca, Boehringer Ingelheim, Medtronik, Novartis, Novo Nordisk, Radcliffe Group, and Vifor Pharma, all outside of the submitted work; and acknowledges non-financial support from the University Hospital Würzburg, and the Comprehensive Heart Failure Center Würzburg, and grant support from BMBF. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Sodium-glucose co-transporter-2 (SGLT2) inhibitors improve clinical outcomes in patients with heart failure (HF), but mechanisms of action are incompletely understood. In the EMPA-TROPISM trial, empagliflozin reversed cardiac remodeling and increased physical capacity in stable non-diabetic patients with systolic HF. Here we explore, post hoc, whether treatment effects in this cohort, comprising patients who had a high prevalence of iron deficiency, were related to iron metabolism. Myocardial iron content estimated by cardiac magnetic resonance T2* quantification increased after initiation of empagliflozin but not placebo (treatment effect: P = 0.01). T2* changes significantly correlated with changes in left ventricular volumes, mass and ejection fraction, peak oxygen consumption and 6-minute walking distance; concomitant changes in red blood cell indices were consistent with augmented hematopoiesis. Exploratory causal mediation analysis findings indicated that changes in myocardial iron content after treatment with empagliflozin may be an important mechanism to explain its beneficial clinical effects in patients with HF.ClinicalTrials.gov: NCT03485222 ., (© 2023. The Author(s).)

Aims: Agonistic antibodies against neurohumoral receptors can induce cardio-noxious effects by altering the baseline receptor activity. To estimate the prevalence of autoantibodies directed against the beta-1 receptor (b1-AAB) in patients admitted to the hospital for acute heart failure (HF) at (i) baseline and (ii) after 6 months of follow-up (F6) and (iii) after another 12 months of follow-up (i.e. 18 months after index hospitalization), to estimate their prognostic impact on clinical outcome (death or first hospitalization for HF)., Methods and Results: In 47 patients, b1-AAB were serially determined in serum samples collected at index hospitalization and at 6 months of follow-up (F6) with a flow cytometry-based assay: median age 71 years (quartiles 60, 80), 23 (49%) women, 24 (51%) HF with preserved ejection fraction. Beta1-AAB were detected in three subjects at index hospitalization (6%), and in eight subjects at F6 (17%). There were no differences apparent between patients with and without b1-AAB at F6 with regard to age, sex, type, duration, or main cause of HF. During the 12 month period following F6 (i.e. up to month 18), eight events occurred. Event-free survival was associated with prevalence of b1-AAB at F6. Compared with patients without b1-AAB at F6, age-adjusted Cox regression indicated a higher event risk in patients harbouring b1-AAB, with a hazard ratio of 8.96 (95% confidence interval 1.81-44.50, P = 0.007)., Conclusions: Our results suggest a possible adverse prognostic relevance of b1-AAB in patients with acute HF, but this observation needs to be confirmed in larger patient collectives., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Hospital admission during nighttime and off hours may affect the outcome of patients with various cardiovascular conditions due to suboptimal resources and personnel availability, but data for acute heart failure remain controversial. Therefore, we studied outcomes of acute heart failure patients according to their time of admission from the global International Registry to assess medical practice with lOngitudinal obseRvation for Treatment of Heart Failure., Methods and Results: Overall, 18 553 acute heart failure patients were divided according to time of admission into 'morning' (7:00-14:59), 'evening' (15:00-22:59), and 'night' (23:00-06:59) shift groups. Patients were also dichotomized to admission during 'working hours' (9:00-16:59 during standard working days) and 'non-working hours' (any other time). Clinical characteristics, treatments, and outcomes were compared across groups. The hospital length of stay was longer for morning (odds ratio: 1.08; 95% confidence interval: 1.06-1.10, P < 0.001) and evening shift (odds ratio: 1.10; 95% confidence interval: 1.07-1.12, P < 0.001) as compared with night shift. The length of stay was also longer for working vs. non-working hours (odds ratio: 1.03; 95% confidence interval: 1.02-1.05, P < 0.001). There were no significant differences in in-hospital mortality among the groups. Admission during working hours, compared with non-working hours, was associated with significantly lower mortality at 1 year (hazard ratio: 0.88; 95% confidence interval: 0.80-0.96, P = 0.003)., Conclusions: Acute heart failure patients admitted during the night shift and non-working hours had shorter length of stay but similar in-hospital mortality. However, patients admitted during non-working hours were at a higher risk for 1 year mortality. These findings may have implications for the health policies and heart failure trials., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Systolic ejection time (SET) is discussed as a treatment target in patients with heart failure (HF) and a reduced left ventricular (LV) ejection fraction (EF). We derived reference values for SET correcting for its dependence on heart rate (SETc), and explored its prognostic utility in patients admitted with decompensated HF., Methods and Results: SETc was derived in 4836 participants of the population-based STAAB study (mean age 55 ± 12 years, 52% women). There, mean SETc was 328 ± 18 ms, increased with age (+4.7 ms per decade), was shorter in men than women (-14.9 ms), and correlated with arterial elastance ( r = 0.30; all P < 0.001). In 134 patients hospitalized with acute HF, SETc at admission was shorter when compared with the general population and differed between patients with HF with reduced EF (HFrEF; LVEF ≤40%; 269 ± 35 ms), HF with mildly reduced EF (HFmrEF; LVEF 41-49%; 294 ± 27 ms), and HF with preserved EF (HFpEF; LVEF ≥50%; 317 ± 35 ms; P < 0.001). In proportional hazard regression, an in-hospital increase in SETc was associated with an age- and sex-adjusted hazard ratio of 0.38 (95% confidence interval 0.18-0.79) in patients with HFrEF, but a hazard ratio of 2.39 (95% confidence interval 1.24-4.64) in patients with HFpEF., Conclusion: In the general population, SETc increased with age and an elevated afterload. SETc was mildly reduced in patients hospitalized with HFpEF, but markedly reduced in patients with HFrEF. In-hospital prolongation of SETc predicted a favourable outcome in HFrEF, but an adverse outcome in HFpEF. Our results support the concept of a U-shaped relationship between cardiac systolic function and risk, providing a rationale for a more individualized treatment approach in patients with HF., Competing Interests: Conflicts of interest: C.M. reports research cooperation with the University of Würzburg and Tomtec Imaging Systems funded by a research grant from the Bavarian Ministry of Economic Affairs, Regional Development and Energy, Germany; advisory and speakers honoraria as well as travel grants from Amgen, Tomtec, Alnylam, Sobi, Alexion, Janssen, Pfizer, and EBR Systems; principal investigator in trials sponsored by Alnylam, AstraZeneca, and Bayer. J.A. reports a clinician scientist scholarship from the Interdisciplinary Center for Clinical Research (IZKF) at the University of Würzburg. G.Ge. reports research cooperation with the University Hospital Würzburg and Tomtec Imaging Systems funded by a research grant from the Bavarian Ministry of Economic Affairs, Regional Development and Energy, Germany. Ch.M. reports honoraria for medical advice and speaker duties from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Berlin Chemie, Bayer, Edwards, NovoNordisk, Novartis, and Servier. S.S. is supported by the CHFC Würzburg, and by the German Federal Ministry of Education and Research (BMBF). He has received consultancy and lecture fees as well as reimbursement of travel costs from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Pfizer, and Servier. The rest of the authors have no conflicts of interest regarding the present work., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Previous reports suggest that risk factors, management, and outcomes of acute heart failure (AHF) may differ by sex, but they rarely extended analysis to low- and middle-income countries., Objectives: In this study, the authors sought to analyze sex differences in treatment and outcomes in patients hospitalized for AHF in 44 countries., Methods: The authors investigated differences between men and women in treatment and outcomes in 18,553 patients hospitalized for AHF in 44 countries in the REPORT-HF (Registry to Assess Medical Practice With Longitudinal Observation for the Treatment of Heart Failure) registry stratified by country income level, income disparity, and world region. The primary outcome was 1-year all-cause mortality., Results: Women (n = 7,181) were older than men (n = 11,372), were more likely to have heart failure with preserved left ventricular ejection fraction, had more comorbid conditions except for coronary artery disease, and had more severe signs and symptoms at admission. Coronary angiography, cardiac stress tests, and coronary revascularization were less frequently performed in women than in men. Women with AHF and reduced left ventricular ejection fraction were less likely to receive an implanted device, regardless of region or country income level. Women were more likely to receive treatments that could worsen HF than men (18% vs 13%; P < 0.0001). In countries with low-income disparity, women had better 1-year survival than men. This advantage was lost in countries with greater income disparity (P interaction  < 0.001)., Conclusions: Women were less likely to have diagnostic testing or receive guideline-directed care than men. A survival advantage for women was observed only in countries with low income disparity, suggesting that equity of HF care between sexes remains an unmet goal worldwide., Competing Interests: Funding Support and Author Disclosures REPORT-HF was funded by Novartis Pharma. Dr Tromp is supported by a National University of Singapore start-up grant, a tier 1 grant from the Ministry of Education, and a CS-IRG New Investigator grant from the National Medical Research Council; has received consulting or speaker fees from Daiichi-Sankyo, Boehringer Ingelheim, Roche Diagnostics, and Us2.ai; and owns patent US-10702247-B2 unrelated to the present work. Dr Angermann has received grant support, personal fees, and nonfinancial support from Abbott, AstraZeneca, Boehringer Ingelheim, Biotronik, Novartis, Novo Nordisk, Radcliffe Group, and Vifor, all outside of the submitted work; nonfinancial support from the University Hospital Würzburg and the Comprehensive Heart Failure Center Würzburg; and grant support from the German Ministry for Education and Research (BMBF). Dr Dahlstrom has received research support from AstraZeneca, Pfizer, Boehringer Ingelheim, Vifor, Roche Diagnostics, and Boston Scientific and speaker honoraria from and consultancies for AstraZeneca, Novartis, and Amgen. Dr Hassanein has received honoraria as a lecturer from Novartis, Aventis, Amgen, Merck Sharp & Dohme, AstraZeneca, and Merck. Drs Ghadanfar, Schweizer, and Obergfell are employed by Novartis. Dr Collins has received research grants from the National Institutes of Health, Agency for Healthcare Research and Quality, and Patient-Centered Outcomes Research Institute and consulting fees from Novartis, Aiphia, Boehringer Ingelheim, Siemens, and Ortho Clinical. Dr Filippatos has received research grants from the European Union, committee fees from Novartis related to REPORT-HF, and committee membership in trials and registries sponsored by Servier, BI, Medtronic, and Vifor. Dr Cleland has received grants and personal fees from Amgen, Bayer, Bristol Myers Squibb, Philips, and Torrent Pharmaceuticals; personal fees from AstraZeneca, Myokardia, Servier, Stealth Biopharmaceuticals, Sanofi, and Abbott; grants, personal fees, and nonfinancial support from Medtronic, Novartis, and Vifor; and grants and nonfinancial support from Pharmacosmos and PharmaNord. Dr Lam is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, and Vifor Pharma; has served as consultant or on the advisory board, steering committee, or executive committee for Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, Vifor Pharma, Novartis, Amgen, Merck, Janssen Research and Development, Menarini, Boehringer Ingelheim, Novo Nordisk, Abbott Diagnostics, Corvia, Stealth BioTherapeutics, JanaCare, Biofourmis, Darma, Applied Therapeutics, MyoKardia, Cytokinetics, WebMD Global, Radcliffe Group, and Corpus; and serves as co-founder and nonexecutive director of eKo.ai. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The importance of chronic kidney disease (CKD) and anaemia has not been comprehensively studied in asymptomatic patients at risk for heart failure (HF) versus those with symptomatic HF. We analysed the prevalence, characteristics and prognostic impact of both conditions across American College of Cardiology/American Heart Association (ACC/AHA) precursor and HF stages A-D., Methods and Results: 2496 participants from three non-pharmacological German Competence Network HF studies were categorized by ACC/AHA stage; stage C patients were subdivided into C1 and C2 (corresponding to NYHA classes I/II and III, respectively). Overall, patient distribution was 8.1%/35.3%/32.9% and 23.7% in ACC/AHA stages A/B/C1 and C2/D, respectively. These subgroups were stratified by the absence ( - ) or presence ( +) of CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73m 2 ) and anaemia (haemoglobin in women/men < 12/ < 13 g/dL). The primary outcome was all-cause mortality at 5-year follow-up. Prevalence increased across stages A/B/C1 and C2/D (CKD: 22.3%/23.6%/31.6%/54.7%; anaemia: 3.0%/7.9%/21.7%/33.2%, respectively), with concordant decreases in median eGFR and haemoglobin (all p < 0.001). Across all stages, hazard ratios [95% confidence intervals] for all-cause mortality were 2.1 [1.8-2.6] for CKD + , 1.7 [1.4-2.0] for anaemia, and 3.6 [2.9-4.6] for CKD + /anaemia + (all p < 0.001). Population attributable fractions (PAFs) for 5-year mortality related to CKD and/or anaemia were similar across stages A/B, C1 and C2/D (up to 33.4%, 30.8% and 34.7%, respectively)., Conclusions: Prevalence and severity of CKD and anaemia increased across ACC/AHA stages. Both conditions were individually and additively associated with increased 5-year mortality risk, with similar PAFs in asymptomatic patients and those with symptomatic HF., (© 2022. The Author(s).)

Competing Interests: I declare personal fees from Abbott for serving as the Chair of the Steering Committee for the CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF) study, which evaluated the CardioMEMS pulmonary artery pressure monitoring technology (manufactured by Abbott). I also disclose consulting fees and speaker honoraria and reimbursement of travel costs from Abbott.

Background: The randomized INH (Interdisciplinary Network Heart Failure) trial (N = 715) reported that 6 months' remote patient management (RPM) (HeartNetCare-HF) did not reduce the primary outcome (time to all-cause death/rehospitalization) vs usual care (UC) in patients discharged after admission for acute heart failure, but suggested lower mortality and better quality of life in the RPM group., Objectives: The Extended (E)-INH trial investigated the effects of 18 months' HeartNetCare-HF on the same primary outcome in an expanded population (N = 1,022) and followed survivors up to 60 months (primary outcome events) or up to 120 months (mortality) after RPM termination., Methods: Eligible patients aged ≥18 years, hospitalized for acute heart failure, and with predischarge ejection fraction ≤40% were randomized to RPM (RPM+UC; n = 509) or control (UC; n = 513). Follow-up visits were every 6 months during RPM, and then at 36, 60, and 120 months., Results: The primary outcome did not differ between groups at 18 months (60.7% [95% CI: 56.5%-65.0%] vs 61.2% [95% CI: 57.0%-65.4%]) or 60 months (78.1% [95% CI: 74.4%-81.6%] vs 82.8% [95% CI: 79.5%-86.0%]). At 60 and 120 months, all-cause mortality was lower in patients previously undergoing RPM (41.1% [95% CI: 37.0%-45.5%] vs 47.4% [95% CI: 43.2%-51.8%]; P = 0.040 and 64.0% [95% CI: 59.8%-68.2%] vs 69.6% [95% CI: 65.6%-73.5%]; P = 0.019). At all visits, health-related quality of life was better in patients exposed to HeartNetCare-HF vs UC., Conclusions: Although 18 months' HeartNetCare-HF did not significantly reduce the primary outcome of death or rehospitalization at 60 months, lower 120-month mortality in patients previously undergoing HeartNetCare-HF suggested beneficial longer-term effects, although the possibility of a chance finding remains., Competing Interests: Funding Support and Author Disclosures This work was funded by Federal Ministry of Education and Research (BMBF), Berlin, Germany, BMBF grant 01GL0304; Competence Network Heart Failure, Berlin, Germany, BMBF grants 01GI0205 and 01GI1202A; and Comprehensive Heart Failure Center Würzburg, Würzburg, Germany, BMBF grants 01EO1004 and 01EO1504. Prof Angermann has received grant support, personal fees, advisory boards, and/or nonfinancial support from Abbott, AstraZeneca, Boehringer Ingelheim, Biotronik, Novartis, ResMed, Thermo Fisher, and Vifor, all outside of the submitted work; has received nonfinancial support from the University Hospital Würzburg and the Comprehensive Heart Failure Center Würzburg; and has received grant support from German BMBF. Ms Sehner has received personal fees from Boston Scientific; and grant support from German BMBF, Atrial Fibrillation NETwork (AFNET), German Centre for Cardiovascular Research, EU Horizon 2020, Adrenomed AG, and Biotronik, outside the submitted work. Dr Güder has received personal fees from AstraZeneca, Abiomed, Bayer, Boehringer Ingelheim, Novartis, Orion GmbH, Pfizer, and Vifor, all outside of the submitted work; and has received grant support from the BMBF, the German Heart Foundation, and the German Cardiac Society. Dr Morbach has received research cooperation with the University of Würzburg and Tomtec Imaging Systems funded by a research grant from the Bavarian Ministry of Economic Affairs, Regional Development and Energy, Germany; has received advisory and speaker honoraria and travel grants from AKCEA, Alnylam, Amgen, Boehringer Ingelheim, EBR Systems, Orion Pharma, Pfizer, SOBI, and Tomtec; has been a principal investigator in trials sponsored by Alnylam, AstraZeneca, and Bayer; and has received financial support from the Interdisciplinary Centre for Clinical Research–IZKF Würzburg (advanced clinician-scientist program). Dr Frantz has received personal fees from Amgen Europe, AstraZeneca, Bayer Vital, Boehringer Ingelheim, Bristol Meyers Squibb GmbH, Daiichi Sankyo, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Sanofi, Servier, and Vifor, all outside of the submitted work; and has received grant support from the BMBF and the German Heart Foundation. Dr Wegscheider has received personal fees from German BMBF, Atrial Fibrillation NETwork (AFNET), German Centre for Cardiovascular Research, EU Horizon 2020, Biotronik, Boston Scientific, and Novartis; and has received grant support from Adrenomed AG and Biotronik, outside the submitted work. Dr Ertl has received personal fees from AstraZeneca, Abbott, Boehringer Ingelheim, Medtronic, Novartis, ResMed, Thermo Fisher, and Vifor; has participated in advisory boards for AstraZeneca, Abbott, Novartis, and Vifor, all outside the submitted work; has received nonfinancial support from the University Hospital Würzburg Comprehensive Heart Failure Center Würzburg; and has received grant support from the German BMBF. Prof Störk has received grant support and/or personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Pfizer, and Sanofi, all outside the submitted work; has received case payments for participation in trials from Akcea, Amgen, AstraZeneca, Bayer, Boehringer, Ionis, Novartis, Pfizer, Sanofi, and Vifor; and has received grant support from the German BMBF, European Union, and University Hospital Würzburg. Dr Faller has reported that he has no relationships relevant to the contents of this paper to disclose. The data that support the findings of this study are available from the corresponding author upon reasonable request., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Effective and safe decongestion remains a major goal for optimal management of patients with acute heart failure (AHF). The effects of the sodium-glucose cotransporter 2 inhibitor empagliflozin on decongestion-related endpoints in the EMPULSE trial (NCT0415775) were evaluated., Methods and Results: A total of 530 patients hospitalized for AHF were randomized 1:1 to either empagliflozin 10 mg once daily or placebo for 90 days. The outcomes investigated were: weight loss (WL), WL adjusted for mean daily loop diuretic dose (WL-adjusted), area under the curve of change from baseline in N-terminal pro-B-type natriuretic peptide levels, hemoconcentration, and clinical congestion score after 15, 30, and 90 days of treatment. Compared with placebo, patients treated with empagliflozin demonstrated significantly greater reductions in all studied markers of decongestion at all time-points, adjusted mean differences (95% confidence interval) at Days 15, 30, and 90 were: for WL -1.97 (-2.86, -1.08), -1.74 (-2.73, -0.74); -1.53 (-2.75, -0.31) kg; for WL-adjusted: -2.31 (-3.77, -0.85), -2.79 (-5.03, -0.54), -3.18 (-6.08, -0.28) kg/40 mg furosemide i.v. or equivalent; respectively (all P < 0.05). Greater WL at Day 15 (i.e. above the median WL in the entire population) was associated with significantly higher probability for clinical benefit at Day 90 (hierarchical composite of all-cause death, heart failure events, and a 5-point or greater difference in Kansas City Cardiomyopathy Questionnaire total symptom score change from baseline to 90 days) with the win ratio of 1.75 (95% confidence interval 1.37, 2.23; P < 0.0001)., Conclusion: Initiation of empagliflozin in patients hospitalized for AHF resulted in an early, effective and sustained decongestion which was associated with clinical benefit at Day 90., Competing Interests: Conflict of interest: A.A.V. has received research support and/or has been a consultant for Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim, Cytokinetics, Merck, Myokardia, Novo Nordisk, Novartis, and Roche Diagnostics. S.P.C. is a consultant for Aiphia, Siemens, Bristol Myers Squibb, Boehringer Ingelheim, and Vixiar and receives research support from the NIH, PCORI, AstraZeneca, and Beckman Coulter. M.N.K. has received research grants from AstraZeneca and Boehringer Ingelheim, and has served as a consultant for Alnylam, AstraZeneca, Amgen, Applied Therapeutics, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Esperion Therapeutics, Janssen, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pharmacosmos, Sanofi, and Vifor. J.R.T. has received research support and/or has been a consultant for Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Medtronic, Merck, Novartis, Servier, and Windtree Therapeutics. C.E.A. has received research support from and/or has been a consultant for Abbott, Boehringer Ingelheim, Medtronic, Novartis, ResMed, Thermo Fisher, Vifor, and German Federal Ministry of Education and Research. J.T. is supported by the National University of Singapore Start-up grant, the tier 1 grant from the ministry of education and the CS-IRG New Investigator Grant from the National Medical Research Council; has received consulting or speaker fees from Daiichi-Sankyo, Boehringer Ingelheim, Roche diagnostics, and Us2.ai, owns patent US-10702247-B2 unrelated to the present work. J.P.F. is a consultant for Boehringer Ingelheim and receives research support from AstraZeneca. M.E.N. has received speaking honoraria from Abbott, and is a consultant for Vifor, Roche, and Amgen. P.P. reports personal fees from Boehringer Ingelheim, AstraZeneca, Servier, Bristol Myers Squibb, Amgen, Novartis, Merck, Pfizer, Berlin Chemie, and grants and personal fees from Vifor Pharma. J.P.B. is an employee of Elderbrook Solutions. M.B. and A.S. are employees of Boehringer Ingelheim. J.B. and M.A.P. have no competing interests., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.)

Aim: The CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF) investigated safety and efficacy of pulmonary artery pressure (PAP)-guided remote patient management (RPM) in New York Heart Association (NYHA) class III outpatients with at least one heart failure hospitalization (HFH) during the previous 12 months. This pre-specified subgroup analysis investigated whether RPM effects depended on presence and subtype of pulmonary hypertension (PH)., Methods and Results: In 106/234 MEMS-HF participants, Swan-Ganz catheter tracings obtained during sensor implant were available for off-line manual analysis jointly performed by two experts. Patients were classified into subgroups according to current PH definitions. Isolated post-capillary PH (IpcPH) and combined post- and pre-capillary PH (CpcPH) were present in 38 and 36 patients, respectively, whereas 31 patients had no PH. Clinical characteristics were comparable between subgroups, but among patients with PH pulmonary vascular resistance was higher (p = 0.029) and pulmonary artery compliance lower (p = 0.003) in patients with CpcPH. During 12 months of PAP-guided RPM, all PAPs declined in IpcPH and CpcPH subgroups (all p < 0.05), whereas only mean and diastolic PAP decreased in patients without PH (both p < 0.05). Improvements in post- versus pre-implant HFH rates were similar in CpcPH (0.639 events/patient-year; hazard ratio [HR] 0.37) and IpcPH (0.72 events/patient-year; HR 0.45) patients. Participants without PH benefited most (0.26 events/patient-year; HR 0.17, p = 0.04 vs. IpcPH/CpcPH patients). Quality of life and NYHA class improved significantly in all subgroups., Conclusions: Outpatients with NYHA class III symptoms with at least one HFH during 1 year pre-implant benefitted significantly from PAP-guided RPM during post-implant follow-up irrespective of presence or subtype of PH at baseline., (© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Patients hospitalized for acute heart failure experience poor health status, including a high burden of symptoms and physical limitations, and poor quality of life. SGLT2 (sodium-glucose cotransporter 2) inhibitors improve health status in chronic heart failure, but their effect on these outcomes in acute heart failure is not well characterized. We investigated the effects of the SGLT2 inhibitor empagliflozin on symptoms, physical limitations, and quality of life, using the Kansas City Cardiomyopathy Questionnaire (KCCQ) in the EMPULSE trial (Empagliflozin in Patients Hospitalized With Acute Heart Failure Who Have Been Stabilized)., Methods: Patients hospitalized for acute heart failure were randomized to empagliflozin 10 mg daily or placebo for 90 days. The KCCQ was assessed at randomization and 15, 30, and 90 days. The effects of empagliflozin on the primary end point of clinical benefit (hierarchical composite of all-cause death, heart failure events, and a 5-point or greater difference in KCCQ Total Symptom Score [TSS] change from baseline to 90 days) were examined post hoc across the tertiles of baseline KCCQ-TSS. In prespecified analyses, changes (randomization to day 90) in KCCQ domains, including TSS, physical limitations, quality of life, clinical summary, and overall summary scores were evaluated using a repeated measures model., Results: In total, 530 patients were randomized (265 each arm). Baseline KCCQ-TSS was low overall (mean [SD], 40.8 [24.0] points). Empagliflozin-treated patients experienced greater clinical benefit across the range of KCCQ-TSS, with no treatment effect heterogeneity (win ratio [95% CIs] from lowest to highest tertile: 1.49 [1.01-2.20], 1.37 [0.94-1.99], and 1.48 [1.00-2.20], respectively; P for interaction=0.94). Beneficial effects of empagliflozin on health status were observed as early as 15 days and persisted through 90 days, at which point empagliflozin-treated patients experienced a greater improvement in KCCQ TSS, physical limitations, quality of life, clinical summary, and overall summary (placebo-adjusted mean differences [95% CI]: 4.45 [95% CI, 0.32-8.59], P =0.03; 4.80 [95% CI, 0.00-9.61], P =0.05; 4.66 [95% CI, 0.32-9.01], P =0.04; 4.85 [95% CI, 0.77-8.92], P =0.02; and 4.40 points [95% CI, 0.33-8.48], P =0.03, respectively)., Conclusions: Initiation of empagliflozin in patients hospitalized for acute heart failure produced clinical benefit regardless of the degree of symptomatic impairment at baseline, and improved symptoms, physical limitations, and quality of life, with benefits seen as early as 15 days and maintained through 90 days., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT0415775.