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BACKGROUND: Initiation and up-titration of guideline-directed medical therapies (GDMT) for heart failure with reduced ejection fraction (HFrEF) remains suboptimal, in part due to concerns regarding tolerability and adverse events (AE). OBJECTIVES: To compare rates of adverse events in patients randomized to GDMT medication vs placebo in a meta-analysis of landmark cardiovascular outcomes trials. METHODS: We assessed rates of reported AE in 17 landmark HFrEF clinical trials across each class of GDMT in the placebo and intervention arms. The overall rates of AE for each drug class, the absolute difference in frequency in AEs between the placebo and intervention arms, and the odds of each AE according based on randomization strata were calculated. RESULTS: AE were reported commonly in trials across each class of GDMT, with 75-85% of participants reporting at least one AE. There was no significant difference in the frequency of AE between the intervention and placebo arms, except for angiotensin converting enzyme (ACE) inhibitors (87.0% [85.0-88.8%] vs 82.0% [79.8-84.0%], absolute difference +5% with intervention, P

Sarcopenia in heart failure (HF) is associated with severe outcomes, increased mortality, and high healthcare cost burden. Systematic muscle screening in patients with chronic HF would improve quality and appropriateness of care. Here we tested handgrip strength (HGS) as a screening tool for sarcopenia in patients with chronic HF, using the EWGSOP 2010 and 2019 reference-standard definitions of sarcopenia.HF inpatients, aged 65 years old or above, were prospectively included between November 2014 and September 2018, and relevant sociodemographic, anthropometric and HF characterization data was collected. The accuracy of HGS as a screening test for sarcopenia was assessed by gender using area under the receiver operating characteristic (ROC) curves (AUC).The population consisted of 118 older patients (age: 78.9 yrs; BMI: 26.6 kg/mHGS can be used as a valid tool to screen for sarcopenia in older (≥65 yrs) patients with chronic HF.NCT03153774.

Cardiogenic shock (CS) with variable systemic inflammation may be responsible for patient heterogeneity and the exceedingly high mortality rate. Cardiovascular events have been associated with clonal haematopoiesis (CH) where specific gene mutations in haematopoietic stem cells lead to clonal expansion and the development of inflammation. This study aims to assess the prevalence of CH and its association with survival in a population of CS patients in a quaternary centre.We compared the frequency of CH mutations among 341 CS patients and 345 ambulatory heart failure (HF) patients matched for age, sex, ejection fraction, and HF aetiology. The association of CH with survival and levels of circulating inflammatory cytokines was analysed. We detected 266 CH mutations in 149 of 686 (22%) patients. CS patients had a higher prevalence of CH-related mutations than HF patients (odds ratio 1.5; 95% confidence interval [CI] 1.0-2.1, p = 0.02) and was associated with decreased survival (30 days: hazard ratio [HR] 2.7; 95% CI 1.3-5.7, p = 0.006; 90 days: HR 2.2; 95% CI 1.3-3.9, p = 0.003; and 3 years: HR 1.7; 95% CI 1.1-2.8, p = 0.01). TET2 or ASXL1 mutations were associated with lower survival in CS patients at all time-points (p ≤ 0.03). CS patients with TET2 mutations had higher circulating levels of SCD40L, interferon-γ, interleukin-4, and tumour necrosis factor-α (p ≤ 0.04), while those with ASXL1 mutations had decreased levels of CCL7 (p = 0.03).Cardiogenic shock patients have high frequency of CH, notably mutations in TET2 and ASXL1. This was associated with reduced survival and dysregulation of circulating inflammatory cytokines in those CS patients with CH.

ImportanceThe diuretic effect of sodium-glucose cotransporter 2 inhibitors may result in interaction with background diuretic therapy in patients with heart failure and preserved ejection fraction (HFpEF).ObjectiveTo assess the safety and efficacy of empagliflozin in combination with background diuretic therapy and the association of empagliflozin with the need for conventional diuretics.Design, Setting, and ParticipantsThis was a post hoc analysis of the Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction (EMPEROR-Preserved). EMPEROR-Preserved was a phase 3, randomized, placebo-controlled, double-blind clinical trial conducted from March 2017 to April 2021. Patients with class II to IV heart failure and left ventricular ejection fraction greater than 40% were included. Of 5988 patients enrolled, 5815 (97.1%) had baseline data on diuretic use and were included in this analysis, which was conducted from November 2021 to August 2022.InterventionsParticipants in EMPEROR-Preserved were randomized to empagliflozin or placebo. In this analysis, participants were divided into 4 subgroups: no diuretics and furosemide-equivalent diuretic dose of less than 40 mg, 40 mg, and greater than 40 mg at baseline.Main Outcomes and MeasuresThe main outcomes of interest were first hospitalization for heart failure (HHF) or cardiovascular death (CV death) and its components. Association of empagliflozin vs placebo with outcomes by baseline diuretic status (no diuretic vs any dose) and dose (no diuretic, 40mg) was assessed. Association of empagliflozin use with changes in diuretic therapy was also studied.ResultsAmong 5815 patients (mean [SD] age, 71.9 [9.4] years; 2594 [44.6%] female) with known baseline diuretic use, 1179 (20.3%) were not taking diuretics, 1725 (29.7%) were taking less than 40 mg, 1772 (30.5%) were taking 40 mg, and 1139 (19.6%) were taking greater than 40 mg. In the placebo arm, patients with higher diuretic doses had worse outcomes. Empagliflozin decreased the risk of HHF or CV death, regardless of background diuretic status (hazard ratio [HR], 0.81; 95% CI, 0.70-0.93] for the diuretic group vs HR, 0.72; 95% CI, 0.48-1.06 for the nondiuretic group; P for interaction = .58). Similarly, diuretic status was not associated with changes in improvements in first HHF, total HHF, rate of decline in estimated glomerular filtration rate, and Kansas City Cardiomyopathy Questionnaire 23 clinical summary score with empagliflozin. Findings were consistent when patients were categorized by diuretic dose. Empagliflozin was associated with a decreased likelihood of diuretic dose escalation (HR, 0.74; 95% CI, 0.65-0.84) and an increased likelihood of de-escalation (HR, 1.15; 95% CI, 1.02-1.30). Empagliflozin was associated with an increased risk of volume depletion in patients taking diuretics (HR, 1.34; 95% CI, 1.13-1.59).ConclusionIn this study, treatment with empagliflozin was similar regardless of diuretic use or dose. Empagliflozin use was associated with decreased conventional diuretic dosing.Trial RegistrationClinicalTrials.gov Identifier: NCT03057951

There is an increasing proportion of the general population surviving to old age with significant chronic disease, multi-morbidity, and disability. The prevalence of pre-frail state and frailty syndrome increases exponentially with advancing age and is associated with greater morbidity, disability, hospitalization, institutionalization, mortality, and health care resource use. Frailty represents a global problem, making early identification, evaluation, and treatment to prevent the cascade of events leading from functional decline to disability and death, one of the challenges of geriatric and general medicine. Cardiac arrhythmias are common in advancing age, chronic illness, and frailty and include a broad spectrum of rhythm and conduction abnormalities. However, no systematic studies or recommendations on the management of arrhythmias are available specifically for the elderly and frail population, and the uptake of many effective antiarrhythmic therapies in these patients remains the slowest. This European Heart Rhythm Association (EHRA) consensus document focuses on the biology of frailty, common comorbidities, and methods of assessing frailty, in respect to a specific issue of arrhythmias and conduction disease, provide evidence base advice on the management of arrhythmias in patients with frailty syndrome, and identifies knowledge gaps and directions for future research. There is an increasing proportion of the general population surviving to old age with significant chronic disease, multi-morbidity, and disability. The prevalence of pre-frail state and frailty syndrome increases exponentially with advancing age and is associated with greater morbidity, disability, hospitalization, institutionalization, mortality, and health care resource use. Frailty represents a global problem, making early identification, evaluation, and treatment to prevent the cascade of events leading from functional decline to disability and death, one of the challenges of geriatric and general medicine. Cardiac arrhythmias are common in advancing age, chronic illness, and frailty and include a broad spectrum of rhythm and conduction abnormalities. However, no systematic studies or recommendations on the management of arrhythmias are available specifically for the elderly and frail population, and the uptake of many effective antiarrhythmic therapies in these patients remains the slowest. This European Heart Rhythm Association (EHRA) consensus document focuses on the biology of frailty, common comorbidities, and methods of assessing frailty, in respect to a specific issue of arrhythmias and conduction disease, provide evidence base advice on the management of arrhythmias in patients with frailty syndrome, and identifies knowledge gaps and directions for future research.

Introduction: Treatment of anemia in dialysis patients has been associated with increased risk of vascular access thrombosis (VAT). Proactive IV irOn Therapy in hemodiALysis Patients (PIVOTAL) was a clinical trial of proactive compared with reactive i.v. iron therapy in patients requiring hemodialysis. We analyzed the trial data to determine whether randomized treatment arm, alongside other clinical and laboratory variables, independently associated with VAT.Methods: In PIVOTAL, 2141 adult patients were randomized. The type of vascular access (arteriovenous fistula [AVF], arteriovenous graft [AVG], or central venous catheter [CVC]) was recorded at baseline and every month after randomization. The associations between clinical and laboratory data and first VAT were evaluated in a multivariate analysis.Results: A total of 480 (22.4%) participants experienced VAT in a median of 2.1 years of follow-up. In multivariable analyses, treatment arm (proactive vs. reactive) was not an independent predictor of VAT (hazard ratio [HR] 1.13, P = 0.18). Diabetic kidney disease (HR 1.45, P < 0.001), AVG use (HR 2.29, P < 0.001), digoxin use (HR 2.48, P < 0.001), diuretic use (HR 1.25, P = 0.02), female sex (HR 1.33, P = 0.002), and previous/current smoker (HR 1.47, P = 0.004) were independently associated with a higher risk of VAT. Angiotensin receptor blocker (ARB) use (HR 0.66, P = 0.01) was independently associated with a lower risk of VAT.Conclusion: In PIVOTAL, VAT occurred in nearly 1 quarter of participants in a median of just >2 years. In this post hoc analysis, randomization to proactive i.v. iron treatment arms did not increase the risk of VAT.

Novel risk stratification and non-invasive surveillance methods are needed in orthotopic heart transplant (OHT) to reduce morbidity and mortality post-transplant. Clonal hematopoiesis (CH) refers to the acquisition of specific gene mutations in hematopoietic stem cells linked to enhanced inflammation and worse cardiovascular outcomes. The purpose of this study was to investigate the association between CH and OHT. Blood samples were collected from 127 OHT recipients. Error-corrected sequencing was used to detect CH-associated mutations. We evaluated the association between CH and acute cellular rejection, CMV infection, cardiac allograft vasculopathy (CAV), malignancies, and survival. CH mutations were detected in 26 (20.5%) patients, mostly in DNMT3A, ASXL1, and TET2. Patients with CH showed a higher frequency of CAV grade 2 or 3 (0% vs. 18%, p .001). Moreover, a higher mortality rate was observed in patients with CH (11 [42%] vs. 15 [15%], p = .008) with an adjusted hazard ratio of 2.9 (95% CI, 1.4-6.3; p = .003). CH was not associated with acute cellular rejection, CMV infection or malignancies. The prevalence of CH in OHT recipients is higher than previously reported for the general population of the same age group, with an associated higher prevalence of CAV and mortality.

Finerenone is a potent and selective mineralocorticoid receptor (MR) antagonist that slowed progression of CKD and reduced risk of CV outcomes vs. placebo in patients with CKD and T2D in the FIDELIO-DKD and FIGARO-DKD phase 3 trials. MR overactivation is involved in DR pathogenesis. To evaluate potential benefits of oral finerenone on progression of DR, two studies of identical observational design (ReFineDR and DeFineDR) retrospectively collected data from patients with DR in FIDELIO-DKD/FIGARO-DKD at selected centers. Eligible patients had a routine ophthalmological examination showing NPDR in ≥1 eye performed 6 months prior to 1 month post-randomization in FIDELIO-DKD/FIGARO-DKD, and ≥1 subsequent ophthalmological assessment. Patients with advanced DR were excluded; inclusion was blinded to FIDELIO-DKD/FIGARO-DKD treatment assignment. Primary endpoint was occurrence of vision-threatening events (ASN, DME or PDR) at 2 years. Overall, 134 patients received finerenone and 1received placebo, of whom 68.7% and 71.8% had mild/moderate NPDR, 3.0% and 10.0% had severe NPDR, 27.6% and 15.5% had NPDR of unknown severity and 70.1% and 64.5% had HbA1c >7.5%, at baseline (mean HbA1c 8.25 [SD 1.41] and 8.18 [SD 1.34]) . At 2 years, 5 (3.7%) and 7 (6.4%) patients in the finerenone and placebo groups had a vision-threatening event in ≥1 eye (difference -0.026, 95% CI -0.082 to 0.029, p=0.3550) . The number of events increased after 2 years, with trends in Kaplan-Meier estimated cumulative incidence probabilities in favor of finerenone at 30 and 36 months (post hoc) . Results were generally consistent across components of the primary endpoint and subgroups with baseline HbA1c ≤ and >7.5%, UACR 30- Disclosure P.Rossing: Consultant; Astellas Pharma Inc., AstraZeneca, Bayer AG, Gilead Sciences, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Speaker's Bureau; Eli Lilly and Company. D.Finis: Employee; Bayer AG. S.Leal: Employee; Bayer Consumer Care AG. T.Schmelter: Employee; Bayer AG, Stock/Shareholder; Bayer AG. G.Bakris: Consultant; Alnylam Pharmaceuticals, Inc., AstraZeneca, DiaMedica Therapeutics, Inc., Horizon Therapeutics plc, Ionis Pharmaceuticals, Merck & Co., Inc., Other Relationship; Novo Nordisk. S.Anker: Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Novartis AG, Novo Nordisk, Vifor Pharma Management Ltd., Research Support; Abbott. J.G.Garweg: Advisory Panel; AbbVie Inc., Research Support; Roche Pharmaceuticals, Speaker's Bureau; Bayer AG, Novartis AG. T.Osonoi: Research Support; Bayer AG, Eli Lilly and Company, Gilead Sciences, Inc., Kowa Company, Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Speaker's Bureau; Novo Nordisk. B.Pitt: Advisory Panel; Merck & Co., Inc., Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Lexicon Pharmaceuticals, Inc., Vifor Pharma Management Ltd. S.Rosas: Advisory Panel; AstraZeneca, Teladoc Health, Other Relationship; Bayer AG, Research Support; AstraZeneca, Bayer AG. L.M.Ruilope: Consultant; Bayer AG. D.Zhu: n/a. M.Brinker: Employee; Bayer AG.

Introduction: Finerenone reduced the risk of cardiovascular (CV) and kidney outcomes, without affecting HbA1c, in CKD and T2D patients in the FIDELITY prespecified pooled analysis of the FIDELIO-DKD and FIGARO-DKD studies. Here, we evaluate the effect of finerenone by baseline HbA1c, HbA1c variability, and diabetes duration. Methods: Patients with T2D and CKD (UACR ≥30-≤5000 mg/g and eGFR ≥25 mL/min/1.73 m2) were randomized to finerenone or placebo. Effects of finerenone vs. placebo on CV (CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and kidney (kidney failure, sustained ≥57% eGFR decline from baseline, or renal death) composite outcomes were analyzed by baseline HbA1c quartiles, HbA1c variability (first year of treatment) , and diabetes duration quartiles. Results: In 13,026 patients included in the analysis, mean baseline HbA1c was 7.7% and diabetes duration was 15.4 years. Higher baseline HbA1c quartiles had longer diabetes duration and more diabetes-related complications. Risk reductions in the CV and kidney composite outcomes with finerenone vs. placebo were consistent across HbA1c (p-interaction 0.52 and 0.09, respectively) and diabetes duration (p-interaction 0.12 and 0.75) quartiles. HbA1c variability in the first year of treatment was associated with higher cardiorenal risks; each 1 unit increase in mean absolute residual of HbA1c was associated with a 20% increased risk of a CV event (HR 1.20; 95% CI 1.07-1.35; p=0.0016) and a 36% increased risk of a kidney event (HR 1.36; 95% CI 1.21-1.52; p Conclusion: Greater variability in HbA1c was associated with increased risks of cardiorenal outcomes. Risk reductions in the CV and kidney outcomes with finerenone in patients with CKD and T2D were not modified by baseline HbA1c, HbA1c variability, or duration of diabetes. Disclosure J. B. Mcgill: Advisory Panel; Gilead Sciences, Inc., Lilly Diabetes, MannKind Corporation, Novo Nordisk A/S, Provention Bio, Inc., Salix Pharmaceuticals, Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; Dexcom, Inc., Novo Nordisk. M. Brinker: Employee; Bayer AG. A. Joseph: Employee; Bayer AG. A. Z. Lage: None. R. Lawatscheck: None. C. Scott: Employee; Bayer AG. P. Rossing: Consultant; Astellas Pharma Inc., AstraZeneca, Bayer AG, Gilead Sciences, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Speaker’s Bureau; Eli Lilly and Company. R. Agarwal: Advisory Panel; Akebia Therapeutics, Inc., Bayer AG, Board Member; Chinook Therapeutics Inc., DiaMedica Therapeutics, Inc., Vertex Pharmaceuticals Incorporated, Consultant; Boehringer Ingelheim International GmbH, Reata Pharmaceuticals, Inc., Vifor Pharma Management Ltd. S. Anker: Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Novartis AG, Novo Nordisk, Vifor Pharma Management Ltd., Research Support; Abbott. G. Bakris: Consultant; Alnylam Pharmaceuticals, Inc., AstraZeneca, DiaMedica Therapeutics, Inc., Horizon Therapeutics plc, Ionis Pharmaceuticals, Merck & Co., Inc., Other Relationship; Novo Nordisk. G. Filippatos: Other Relationship; Amgen Inc., Amgen Inc., Bayer AG, Boehringer Ingelheim International GmbH, Medtronic, Novartis AG, Servier Laboratories, Vifor Pharma Management Ltd. B. Pitt: Advisory Panel; Merck & Co., Inc., Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Lexicon Pharmaceuticals, Inc., Vifor Pharma Management Ltd. L. M. Ruilope: Consultant; Bayer AG. A. L. Birkenfeld: None. L. Caramori: Advisory Panel; Bayer AG, Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk, Research Support; Bayer AG, Novartis AG.

Introduction: Finerenone reduced risk of cardiorenal outcomes in patients with CKD and T2D in the FIDELIO-DKD and FIGARO-DKD studies. In FIDELIO-DKD the effects of finerenone on kidney and CV outcomes were consistent irrespective of glucagon-like peptide-1 receptor agonist (GLP-1RA) use, but analyses were better powered to evaluate change in urine albumin-to-creatinine ratio (UACR) . Here, we extend these analyses to patients in both studies (FIDELITY analysis) , thus encompassing a larger population with broader inclusion criteria. Methods: Patients with T2D and CKD (UACR ≥30- Results: Of 13026 patients, 944 (7.2%) received GLP-1RAs at baseline. Results were consistent irrespective of GLP-1RA use at baseline for the CV composite outcome (hazard ratio [HR] 0.76; 95% CI 0.52-1.with GLP-1RA; HR 0.87, 95% CI 0.79-0.96 without GLP-1RA; p-interaction 0.63) , and the kidney composite outcome (HR 0.82; 95% CI 0.45-1.48 with GLP-1RA; HR 0.77, 95% CI 0.67-0.89 without GLP-1RA; p-interaction 0.79) . A greater reduction in UACR was observed with finerenone in patients taking GLP-1RA at baseline (placebo-corrected change -38% with GLP-1RA and -31% without GLP-1RA use; p-interaction 0.03) . Incidence of hyperkalemia was similarly increased with finerenone irrespective of GLP-1RA use at baseline. Conclusion: The benefits of finerenone on composite CV and kidney outcomes in patients with CKD and T2D are not modified by GLP-1RA use at baseline, with an increased effect observed for UACR reduction, suggesting a different mechanism of reduction in albuminuria. Disclosure P.Rossing: Consultant; Astellas Pharma Inc., AstraZeneca, Bayer AG, Gilead Sciences, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Speaker's Bureau; Eli Lilly and Company. P.Viswanathan: Employee; Bayer AG. R.Lawatscheck: None. A.Joseph: Employee; Bayer AG. G.Bakris: Consultant; Alnylam Pharmaceuticals, Inc., AstraZeneca, DiaMedica Therapeutics, Inc., Horizon Therapeutics plc, Ionis Pharmaceuticals, Merck & Co., Inc., Other Relationship; Novo Nordisk. S.Anker: Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Novartis AG, Novo Nordisk, Vifor Pharma Management Ltd., Research Support; Abbott. G.Filippatos: Other Relationship; Amgen Inc., Amgen Inc., Bayer AG, Boehringer Ingelheim International GmbH, Medtronic, Novartis AG, Servier Laboratories, Vifor Pharma Management Ltd. B.Pitt: Advisory Panel; Merck & Co., Inc., Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Lexicon Pharmaceuticals, Inc., Vifor Pharma Management Ltd. L.M.Ruilope: Consultant; Bayer AG. V.Fonseca: Consultant; Abbott, Asahi Kasei Corporation, Bayer AG, Novo Nordisk, Sanofi, Research Support; Fractyl Health, Inc., Jaguar Gene Therapy, Stock/Shareholder; Abbott, Amgen Inc., BRAVO4Health, Mellitus Health. G.E.Umpierrez: Research Support; AstraZeneca, Dexcom, Inc., Novo Nordisk. L.Caramori: Advisory Panel; Bayer AG, Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk, Research Support; Bayer AG, Novartis AG. M.Lambelet: Other Relationship; Bayer AG.

Aims Empagliflozin reduces the risk of cardiovascular death or heart failure (HF) hospitalization in patients with HF and preserved ejection fraction. This study aims to evaluate if systolic blood pressure (SBP) moderates these effects. Methods and results The association of SBP and the treatment effects of empagliflozin in EMPEROR-Preserved (empagliflozin outcome trial in patients with chronic heart failure with preserved ejection fraction) was evaluated. Randomized patients (n = 5988) were grouped according to SBP at baseline ( 130 mmHg, n = 3118). The effect of empagliflozin on blood pressure, cardiovascular death or HF hospitalization (primary outcome), total HF hospitalizations, and rate of decline in estimated glomerular filtration rate was studied. Over a median of 26.2 months, the placebo-corrected decline was small and not significantly different across baseline SBP. On placebo, the risk of cardiovascular death or hospitalization for HF was 8.58 at >130 mmHg, 8.26 at 110–130 mmHg, and 11.59 events per 100 patient-years at 130 mmHg, P = 0.08 vs. 110–130 mmHg). There was no evidence for baseline SBP moderating the effect of empagliflozin on risk of HF events (primary endpoint interaction P = 0.69, recurrent HF hospitalizations interaction P = 0.55). When comparing empagliflozin with placebo, SBP did not meaningfully associate with adverse events such as hypotension, volume depletion, and acute renal failure. Conclusion In EMPEROR-Preserved, empagliflozin was effective and safe without SBP meaningfully moderating empagliflozin’s treatment effects. This analysis of EMPEROR-Preserved shows that empagliflozin can be used safely and effectively without blood pressure being a meaningful moderator of the drug benefit. Clinical Trial Registration URL: https://www.clinicaltrials.gov Unique identifier: NCT03057951

BACKGROUND: People with kidney failure treated with hemodialysis (HD) are at increased risk of stroke compared with similarly aged people with normal kidney function. One concern is that treatment of renal anemia might increase stroke risk. We studied risk factors for stroke in a prespecified secondary analysis of a randomized, controlled trial of intravenous iron treatment strategies in HD. METHODS: We analyzed data from the Proactive IV Iron Therapy in Haemodialysis Patients (PIVOTAL) trial, focusing on variables associated with risk of stroke. The trial randomized 2141 adults who had started HD

Introduction: Patients with CKD and T2D are at high risk of morbidity and mortality despite the use of guideline-directed therapies. Finerenone, a novel, selective, nonsteroidal mineralocorticoid receptor antagonist, reduced the risk of adverse kidney and CV outcomes in patients with CKD and T2D; here we report outcomes by baseline A1C. Methods: FIDELIO-DKD (NCT02540993) randomized 5734 patients from 48 countries to receive oral finerenone or placebo. Eligible patients had T2D, with a UACR of ≥30-≤5000 mg/g, eGFR ≥25‍-‍12% at screening were excluded. The primary outcome was a composite of kidney failure, sustained ≥40% decrease in eGFR from baseline, or renal death. The key secondary outcome was a composite of CV death, non-fatal MI, non-fatal stroke, or hospitalization for HF. Results: In the 5674 patients analyzed, the mean baseline A1C was 7.7% and mean diabetes duration was 16.6 years; finerenone did not affect A1C during the trial. Overall, 2948 patients had A1C ≤7.5% and 2715 patients had A1C >7.5% at baseline. Patients with higher A1C levels were more likely to use insulin and had a longer duration of diabetes. After a median follow-up of 2.6 years, the primary outcome occurred in fewer patients treated with finerenone compared with placebo, this was observed in both the A1C ≤7.5% and >7.5% groups (18.7% vs. 21.5% patients with A1C of ≤7.5% [HR 0.86; 95% CI 0.73-1.01]; 16.9% vs. 20.7% patients with A1C >7.5% [HR 0.79; 95% CI 0.66-0.94]; P-interaction 0.47). Finerenone also reduced the incidence of the key secondary CV outcome compared with placebo regardless of baseline A1C (HR 0.88; 95% CI 0.71-1.07 for A1C ≤7.5% and HR 0.83; 95% CI 0.69-1.01 for A1C >7.5%; P-interaction 0.73). Reduction in UACR was consistent across subgroups. Overall, hyperkalemia events were independent of A1C level. Conclusion: In patients with CKD and T2D, treatment with finerenone reduced the risk for developing adverse kidney and CV outcomes independent of baseline A1C. Disclosure P. Rossing: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Merck KGaA, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Vifor Pharma Management Ltd. M. Brinker: Employee; Self; Bayer AG, Stock/Shareholder; Self; Bayer AG. C. Scott: Employee; Self; Bayer PLC. G. Bakris: Consultant; Self; Alnylam Pharmaceuticals, Inc., Bayer AG, Ionis Pharmaceuticals, Merck & Co., Inc., Vascular Dynamics Inc. E. Burgess: Advisory Panel; Self; Bayer Inc. R. Agarwal: Advisory Panel; Self; Akebia Therapeutics, Inc., Bayer Healthcare Pharmaceuticals Inc., Diamedica, Relypsa Inc., Sanofi US, Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Reata Pharmaceuticals, Inc., Other Relationship; Self; AstraZeneca, Chinook. S. Anker: Consultant; Self; Abbott, Bayer AG, Boehringer Ingelheim International GmbH, Cardiac Dimensions Pty. Ltd., Impulse Dynamics, Novartis AG, Servier Laboratories, Vifor Pharma Management Ltd., Other Relationship; Self; Abbott, Vifor Pharma Management Ltd. G. Filippatos: Other Relationship; Self; Bayer AG, Boehringer Ingelheim International GmbH, Servier Laboratories. B. Pitt: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Consultant; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Lexicon Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Sanofi. L. M. Ruilope: None. P. Gillard: None. A. Joseph: Employee; Self; Bayer AG. Funding Bayer AG

Aims: It is largely unknown whether cancer patients seen in routine care show ventricular arrhythmias in 24 h electrocardiograms (ECGs), and whether when they are detected they carry prognostic relevance. Methods and Results: We included 261 consecutive cancer patients that were referred to the department of cardiology for 24 h ECG examination and 35 healthy controls of similar age and sex in the analysis. To reduce selection bias, cancer patients with known left ventricular ejection fraction

Introduction The most common type of central sleep apnea (CSA) breathing pattern in patients with heart failure (HF) is Cheyne-Stokes respiration (CSR). CSR manifests as a cyclical pattern of apnea and hyperventilation, with absence of airflow and respiratory effort followed by hyperventilation in a crescendo-decrescendo pattern. CSR may be a predictor of negative clinical outcomes in HF patients. Purpose Examine the response to transvenous phrenic nerve stimulation (TPNS) in patients with HF and different amounts of CSR. Methods Patients with CSA and HF who participated in the remedē System Pivotal Trial were divided into clinically relevant subgroups based on percentage of sleep in CSR (%CSR: 50%) during their baseline polysomnogram. The subgroups were analyzed for efficacy and safety by randomized group (TPNS vs control [no TPNS]). Epworth sleepiness scale (ESS) was also collected. Results At baseline, higher percentage CSR subgroups had lower left ventricular ejection fraction (median 45% for CSR 50%). Baseline apnea-hypopnea index (AHI) indicated severe CSA in all subgroups. All CSR subgroups receiving TPNS therapy had more than 50% of patients achieve ≥50% reduction in AHI at 6 months (see Table); control response rates were ≤11% in each CSR subgroup. The AHI decreased by ≥21 events/hour in each CSR subgroup on therapy while Control subgroups had little or no improvement. The central apnea index decreased to median ≤3 events/hour in each TPNS CSR subgroup; each control subgroup had median 22-24 events/hour remaining at 6 months. Baseline daytime sleepiness was worse in lower %CSR subgroups, however improved in all subgroups. No apparent relationship existed between %CSR and cardiovascular death in patients using TPNS therapy through 6 months, with the only death being in the 20-50% CSR subgroup; the death was determined not related to device, therapy or procedure by the clinical events committee. Further, 2/22 control subjects with CSR>50% experienced a cardiovascular death compared to 0/12 in the TPNS treated subgroup. Conclusions Transvenous phrenic nerve stimulation can treat CSA in HF patients regardless of the percentage of sleep in CSR and no signal of increased mortality was observed.

AIMS: Insulin resistance (IR) is a characteristic feature of heart failure (HF) pathophysiology that affects symptoms and mortality. Differences in the pathophysiological profile of IR in HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) are not characterized in detail. The aim of this study was to evaluate features of IR in HFpEF vs. HFrEF. METHODS AND RESULTS: We included 18 patients with HFrEF (EF 30 +/- 11%, body mass index (BMI) 26.5 +/- 3.3 kg/m2 ), 22 HFpEF patients (EF 63 +/- 7%, BMI 28.6 +/- 4.8 kg/m2 ), and 20 healthy controls of similar age, all without diabetes mellitus. Patients were in stable ambulatory condition and on stable medical regimens for HF. IR was assessed at fasting steady state by the homeostasis model assessment (HOMA) index and within the physiological range of insulin-glucose interactions by the short insulin sensitivity test (SIST). Fasting-state IR was observed in HFpEF and in HFrEF in comparison with controls (HOMA 1.9, interquartile range (IQR) 1.5-3.6 vs. HOMA 3.1, IQR 1.4-3.7 vs. controls 1.2, IQR 1.8-0.9, respectively; analysis of variance P < 0.001), but no statistical difference was observed between HFpEF and HFrEF. The dynamic test over the physiological range of insulin-glucose interactions revealed a more severe IR in HFrEF as compared with HFpEF. Thus, glucose levels remained the highest in HFrEF (76 (64-89) mg/dL) at the end of the SIST compared with HFpEF and controls (68 (58-79) and 56 (44-66) mg/dL, respectively, P < 0.001). CONCLUSION: IR is present in non-diabetic patients with HFpEF and HFrEF. However, distinct differences in the insulin sensitivity characteristics in HFpEF and HFrEF become apparent by more advanced testing. Patients with HFrEF showed more severe IR.

Aims Uncertainties remain on the biological and prognostic significance and therapeutic implications of loss in body weight (W-LOSS) in chronic heart failure (HF) patients. We assessed whether W-LOSS added additional prognostic value to classical clinical risk factors in two separate and large cohorts of patients with chronic HF. The factors associated with W-LOSS were studied. Methods and results W-LOSS and estimated plasma volume changes were measured serially in the GISSI-HF (n = 6820) and Val-HeFT trials (n = 4892). In both studies, experiencing at least one episode of ≥5% W-LOSS during the first year of follow-up was considered a sign of wasting. In GISSI-HF, self-reported unintentional W-LOSS ≥2 kg between two consecutive clinical visits within 1 year was also considered a sign of wasting. W-LOSS occurred in 16.4% and 15.7% of the patients enrolled in GISSI-HF and Val-HeFT, respectively (unintentional ≥2 kg W-LOSS occurred in 18.9% in GISSI-HF). In multivariable analyses adjusting for a number of baseline covariates as well as for plasma volume changes, W-LOSS was found to be independently associated with mortality and adverse cardiovascular and non-cardiovascular outcomes, with a significant net reclassification improvement (cfNRI) and an increase in integrated discrimination improvement (IDI). W-LOSS was independently associated with several features representing the severity of HF, including baseline NT-proBNP and high sensitivity C-reactive protein (hsCRP) in Val-HeFT. Conclusions W-LOSS was a frequent finding in the GISSI-HF and Val-HeFT trials, associated with multiple patient features, and added additional prognostic information beyond clinical variables of HF severity, including estimated plasma volume changes.

BACKGROUND: Isolated systolic hypertension (ISH) is common in older adults and is a risk factor for incident heart failure (HF). We examined the association of systolic-diastolic hypertension (SDH) with incident HF and other outcomes in older adults. METHODS: In the Cardiovascular Health Study (CHS), 5776 community-dwelling adults ≥65 years had data on baseline systolic and diastolic blood pressure (SBP and DBP). We excluded those with DBP

Aims The aim of this document was to obtain a real-life contemporary analysis of the demographics and heart failure (HF) statistics, as well as the organization and major activities of the Heart Failure National Societies (HFNS) in European Society of Cardiology (ESC) member countries. Methods and results Data from 33 countries were collected from HFNS presidents/representatives during the first Heart Failure Association HFNS Summit (Belgrade, Serbia, 29 October 2011). Data on incidence and/or prevalence of HF were available for 22 countries, and the prevalence of HF ranged between 1% and 3%. In five European and one non-European ESC country, heart transplantation was reported as not available. Natriuretic peptides and echocardiography are routinely applied in the management of acute HF in the median of 80% and 90% of centres, respectively. Eastern European and Mediterranean countries have lower availability of natriuretic peptide testing for acute HF patients, compared with other European countries. Almost all countries have organizations dealing specifically with HF. HFNS societies for HF patients exist in only 12, while in 16 countries HF patient education programmes are active. Most HFNS reported that no national HF registry exists in their country. Fifteen HFNS produced national HF guidelines, while 19 have translated the ESC HF guidelines. Most HFNS (n = 23) participated in the organization of the European HF Awareness Day. Conclusion This document demonstrated significant heterogeneity in the organization of HF management, and activities of the national HF working groups/associations. High availability of natriuretic peptide and echocardiographic measurements was revealed, with differences between developed countries and countries in transition.

Aims Midregional pro atrial natriuretic peptide (MR-proANP) is useful for diagnosing acute heart failure (HF) in patients presenting to the Emergency Department with dyspnoea. Optimal interpretation of MR-proANP requires understanding of how various demographic variables influence its levels and performance as a diagnostic marker. We sought to determine how age, race, sex, and body mass index (BMI) affect the levels and interpretation of MR-proANP for the diagnosis of acute HF. Methods and results The Biomarkers in Acute Heart Failure (BACH) study was an international 15-centre study of 1641 patients presenting to the Emergency Department with acute dyspnoea. Of these, 1352 had complete information on age, race, sex, and BMI. MR-proANP levels increased with age and were higher in men and in patients with lower BMI. MR-proANP performed better as a diagnostic marker in younger individuals and in blacks compared with whites. Despite this, MR-proANP at the recommended cut-off point of 120 pmol/L was >90 % sensitive in ruling out the diagnosis of acute HF in all subgroups of patients except white subjects

Few tools exist that provide objective accurate prediction of short-term mortality risk in patients presenting with acute heart failure (AHF). The purpose was to describe the accuracy of several biomarkers for predicting short-term death rates in patients diagnosed with AHF in the emergency department (ED).

Nach dem Fasziendistorsionsmodell des amerikanischen Osteopathen Stephen Typaldos liegen den Beschwerden 6 unterschiedliche fasziale Distorsionen zugrunde, die einzeln oder in Kombination auftreten konnen. Die Beschreibung der Beschwerden durch den Patienten und dessen Korpersprache ermoglichen eine exakte Zuordnung zur jeweiligen Distorsion und damit deren erfolgreiche manuelle Behandlung.

In diesem Beitrag wird die systematische Untersuchung des Bruckenbestands des Landes Mecklenburg-Vorpommern hinsichtlich seiner Gefahrdung durch Spannungsrisskorrosion beschrieben. Das Projekt war in vier Phasen gegliedert. Zunachst wurde ein Konzept erarbeitet, danach aus dem gesamten Bruckenbestand die gefahrdeten Bauwerke herausgefiltert und in Kategorien bzw. Bauwerksgruppen eingeteilt. 16 besonders gefahrdete Brucken wurden genauer untersucht. In der zweiten Phase wurden die Erkenntnisse aus dieser 1. Phase auf den gesamten Bauwerksbestand ubertragen und eine Prioritatenliste erstellt. Auserdem fanden Beprobungen erster ausgewahlter Bauwerke statt. Auf die Phasen 3 und 4, bei denen weiterfuhrende theoretische Untersuchungen fur spezielle Bauwerke im Vordergrund stehen, wird in diesem Beitrag nicht naher eingegangen. Hazard stress corrosion cracking – Systematical analysis of bridges in Mecklenburg-Vorpommern. In this article, the systematic investigation of all prestressed bridges of Mecklenburg-Vorpommern with regard to its exposure to stress corrosion cracking is described. The project was divided into four phases. First, a generally concept was developed. Then the endangered buildings were divided into categories. 16 bridges have been investigated. In the second phase, the findings from phase 1 have been transferred to all buildings in the stock and a priority list drawn up. In addition, first bridges were sampled. In the phase 3 and 4 were more theoretical studies and specific buildings in the foreground. These phases are not content of this paper.

Heart failure is a serious condition and equivalent to malignant disease in terms of symptom burden and mortality. At this moment only a comparatively small number of heart failure patients receive specialist palliative care. Heart failure patients may have generic palliative care needs, such as refractory multifaceted symptoms, communication and decision making issues and the requirement for family support. The Advanced Heart Failure Study Group of the Heart Failure Association of the European Society of Cardiology organized a workshop to address the issue of palliative care in heart failure to increase awareness of the need for palliative care. Additional objectives included improving the accessibility and quality of palliative care for heart failure patients and promoting the development of heart failure-orientated palliative care services across Europe. This document represents a synthesis of the presentations and discussion during the workshop and describes recommendations in the area of delivery of quality care to patients and families, education, treatment coordination, research and policy.

Midregion proadrenomedullin (MR-proADM) was shown to predict 90-day mortality in shortness of breath in the BACH (Biomarkers in Acute Heart Failure) study. Recent studies have demonstrated that serial measurement of MR-proADM, B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) may

GLP-1 receptor agonists have antihypertensive properties, explained via release of atrial natriuretic peptide (ANP) as shown in mice (1). Whether GLP-1 directly interacts with the natriuretic peptide system in humans was studied in a single report (2). Here, we studied interaction of two major incretins, glucose-dependent insulinotropic peptide (GIP) and GLP-1, both administered exogenously, with ANP in patients with type 2 diabetes (nine men and three women, 61 ± 10 years, BMI 30.0 ± 3.7 kg/m2, HbA1c 7.3 ± 1.5%). Placebo (vehicle: 0.9% NaCl with 1% human serum albumin), GIP (4 pmol · kg−1 · min−1), GLP-1(7–36)-amide (1.2 pmol · kg−1 · min−1), or a combination of both hormones were infused over 360 min on different days in randomized order (3). Additionally, eight male overweight subjects with normal glucose tolerance (49.9 ± 3.2 years, BMI 32.9 ± 0.7 kg/m2) were given GIP infusion (2 pmol · kg−1 · min−1) and placebo (isotonic saline) infusion for 240 min (4). In cohort I, intact, biologically active GIP and GLP-1 were measured as described previously (3). In cohort II, total GIP was determined by commercial ELISA kit (Linco Research, St. Charles, MO). Midregional pro-ANP (MR-proANP) was measured with an immunoassay (MR-proANP LIA; B.R.A.H.M.S GmbH, Hennigsdorf, Germany). In subjects with type 2 diabetes, exogenous GIP elevated the total concentrations of GIP …

Background: Among older adults