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Aims: The prevalence of iron deficiency (ID) in newly diagnosed heart failure (HF) and the progression of ID in patients after initiation of HF therapy are unknown. We aimed to describe the natural trajectory of ID in patients with new onset HF during the first year after HF diagnosis, assessing associations between ID, clinical factors, and quality of life (QoL). Methods and results: A prospective cohort of patients with new onset HF in hospitals or outpatient clinics at five major hospitals in Stockholm, Sweden, during 2015–2018 were analysed with clinical assessment, electrocardiogram, blood samples including iron levels, Minnesota living with heart failure questionnaire (MLHFQ), and echocardiogram at baseline and after 12 months. Of 547 patients with new‐onset HF, 482 (88%) had complete iron data at baseline. Median age was 70 years (interquartile range 61–77) and 311 (65%) were men; 55% of patients had ejection fraction (EF) ≤ 40%, 19% had EF 41–49%, and 26% had HF with preserved EF (HFpEF) [Correction added on 26 June 2024, after first online publication: The 'Mean age was 70 years' has been corrected to 'Median age was 70 years' in this version.]. At baseline, 163 patients (34%) had ID defined as ferritin <100 μg/L or ferritin 100–299 μg/L and transferrin saturation <20%. After 12 months of follow‐up, 119 (32%) had ID of the 368 patients who had complete iron data both at baseline and after 12 months and did not receive intravenous (i.v.) iron during follow‐up. During the first year after HF diagnosis, 19% had persistent ID, 13% developed ID, 11% resolved ID, and 57% never had ID, consequently 24% changed their classification. Anaemia at baseline was the strongest independent predictor of ID 1 year after diagnosis [odds ratio (OR) 3.91, 95% confidence interval (CI) 1.88–8.13, P < 0.001], followed by HF hospitalization (OR 2.21, 95% CI 1.24–3.95, P < 0.01), female sex (OR 2.04, 95% CI 1.25–3.32, P < 0.01), HFpEF (OR 1.96, 95% CI 1.13–3.39, P < 0.05), and diabetes mellitus (OR 1.92, 95% CI 1.06–3.48, P < 0.05). ID was associated with low QoL at baseline (MLHFQ score mean difference 7.4 points, 95% CI 3.1–11.7, P < 0.001), but not at follow‐up. Conclusions: About one third of patients with new onset HF had ID both at the time of HF diagnosis and after 1 year, though a quarter of the patients changed their ID status. Patients with anaemia, HF hospitalization, female gender, HFpEF, or diabetes mellitus at baseline were more likely to have ID after 1 year implying that these should be carefully screened for ID to find those in need of i.v. iron treatment. [ABSTRACT FROM AUTHOR]

Aims: Patients with heart failure usually have several other medical conditions that might alter the effects of interventions. We investigated whether the burden of comorbidity modified the clinical response to cardiac resynchronization therapy (CRT). Methods and results: Original patient‐level data from eight randomized trials exploring the effects of CRT versus no CRT were pooled (BLOCK‐HF, MIRACLE, MIRACLE‐ICD, MIRACLE‐ICD II, RAFT, COMPANION, MADIT‐CRT and REVERSE). A prior history of the following comorbidities was considered: episodic or persistent atrial fibrillation (n = 920), coronary artery disease (n = 3732), diabetes (n = 2171), and hypertension (n = 3353). Patients were classified into three groups based on the number of comorbidities: 0, 1–2, or ≥3. The outcomes of interest were time to all‐cause mortality and time to the composite outcome of heart failure hospitalization (HFH) or all‐cause mortality. Outcomes were evaluated within each comorbidity group using a Bayesian hierarchical Weibull survival regression model. Of 6324 patients, 970 (15%) had no comorbidities, 4052 (64%) had 1–2 and 1302 (21%) had ≥3 comorbidities. The adjusted hazard ratio (aHR) for CRT versus no CRT for all‐cause mortality in the overall cohort was 0.79 (95% credible interval [CI] 0.68–0.93) (p = 0.010); for no comorbidities the aHR was 0.54 (95% CI 0.34–0.86), for 1–2 comorbidities was 0.81 (95% CI 0.67–0.97) and for ≥3 comorbidities was 0.83 (95% CI 0.64–1.07) (no significant interaction between CRT and comorbidity burden: p = 0.13). For the endpoint of HFH or all‐cause mortality, the aHR for the overall cohort was 0.74 (95% CI 0.65–0.84) (p = 0.001), for no comorbidities was 0.69 (95% CI 0.50–0.94), for 1–2 comorbidities was 0.77 (95% CI 0.66–0.90) and for ≥3 comorbidities was 0.68 (95% CI 0.55–0.82) (no significant interaction between CRT and comorbidity burden: p = 0.081). Conclusion: In a meta‐analysis of patient‐level data from eight major trials, the totality of evidence suggests that CRT reduces HFH and/or all‐cause mortality even when several comorbid diseases are present. Clinical Trial Registration: NCT00271154, NCT00251251, NCT00267098, NCT00180271. [ABSTRACT FROM AUTHOR]

Implantable devices form an integral part of the management of patients with heart failure (HF) and provide adjunctive therapies in addition to cornerstone drug treatment. Although the number of these devices is growing, only few are supported by robust evidence. Current devices aim to improve haemodynamics, improve reverse remodelling, or provide electrical therapy. A number of these devices have guideline recommendations and some have been shown to improve outcomes such as cardiac resynchronization therapy, implantable cardioverter‐defibrillators and long‐term mechanical support. For others, more evidence is still needed before large‐scale implementation can be strongly advised. Of note, devices and drugs can work synergistically in HF as improved disease control with devices can allow for further optimization of drug therapy. Therefore, some devices might already be considered early in the disease trajectory of HF patients, while others might only be reserved for advanced HF. As such, device therapy should be integrated into HF care programmes. Unfortunately, implementation of devices, including those with the greatest evidence, in clinical care pathways is still suboptimal. This clinical consensus document of the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC) describes the physiological rationale behind device‐provided therapy and also device‐guided management, offers an overview of current implantable device options recommended by the guidelines and proposes a new integrated model of device therapy as a part of HF care. [ABSTRACT FROM AUTHOR]

Background: The response to cardiac resynchronization therapy (CRT) depends on septal viability and correction of abnormal septal motion. This study investigates if cardiac magnetic resonance (CMR) as a single modality can identify CRT responders with combined imaging of pathological septal motion (septal flash) and septal scar. Methods: In a prospective, multicenter, observational study of 136 CRT recipients, septal scar was assessed using late gadolinium enhancement (LGE) (n = 127) and septal flash visually from cine CMR sequences. The primary endpoint was CRT response, defined as ≥15% reduction in LV end-systolic volume with echocardiography after 6 months. The secondary endpoint was heart transplantation or death of any cause assessed after 39 ± 13 months. Results: Septal scar and septal flash were independent predictors of CRT response in multivariable analysis (both p < 0.001), while QRS duration and morphology were not. The combined approach of septal scar and septal flash predicted CRT response with an area under the curve of 0.86 (95% confidence interval (CI): 0.78–0.94) and was a strong predictor of long-term survival without heart transplantation (hazard ratio 0.27, 95% CI: 0.10–0.79). The accuracy of the approach was similar in the subgroup with intermediate (130–150 ms) QRS duration. The combined approach was superior to septal scar and septal flash alone (p < 0.01). Conclusions: The combined assessment of septal scar and septal flash using CMR as a single-image modality identifies CRT responders with high accuracy and predicts long-term survival. [ABSTRACT FROM AUTHOR]

Aims: To investigate the association of cardiac resynchronization therapy (CRT) on outcomes among participants with and without a history of atrial fibrillation (AF). Methods: Individual‐patient‐data from four randomized trials investigating CRT‐Defibrillators (COMPANION, MADIT‐CRT, REVERSE) or CRT‐Pacemakers (COMPANION, MIRACLE) were analyzed. Outcomes were time to a composite of heart failure hospitalization or all‐cause mortality or to all‐cause mortality alone. The association of CRT on outcomes for patients with and without a history of AF was assessed using a Bayesian‐Weibull survival regression model adjusting for baseline characteristics. Results: Of 3964 patients included, 586 (14.8%) had a history of AF; 2245 (66%) were randomized to CRT. Overall, CRT reduced the risk of the primary composite endpoint (hazard ratio [HR]: 0.69, 95% credible interval [CI]: 0.56–0.81). The effect was similar (posterior probability of no interaction = 0.26) in patients with (HR: 0.78, 95% CI: 0.55–1.10) and without a history of AF (HR: 0.67, 95% CI: 0.55–0.80). In these four trials, CRT did not reduce mortality overall (HR: 0.82, 95% CI: 0.66–1.01) without evidence of interaction (posterior probability of no interaction = 0.14) for patients with (HR: 1.09, 95% CI: 0.70–1.74) or without a history of AF (HR: 0.70, 95% CI: 0.60–0.97). Conclusion: The association of CRT on the composite endpoint or mortality was not statistically different for patients with or without a history of AF, but this could reflect inadequate power. Our results call for trials to confirm the benefit of CRT recipients with a history of AF. [ABSTRACT FROM AUTHOR]

Cardiac resynchronization therapy (CRT) was proposed in the 1990s as a new therapy for patients with heart failure and wide QRS with depressed left ventricular ejection fraction despite optimal medical treatment. This review is aimed first to describe the rationale and the physiologic effects of CRT. The journey of the landmark randomized trials leading to the adoption of CRT in the guidelines since 2005 is also reported showing the high level of evidence for CRT. Different alternative pacing modalities of CRT to conventional left ventricular pacing through the coronary sinus have been proposed to increase the response rate to CRT such as multisite pacing and endocardial pacing. A new emerging alternative technique to conventional biventricular pacing, conduction system pacing (CSP), is a promising therapy. The different modalities of CSP are described (Hirs pacing and left bundle branch area pacing). This new technique has to be evaluated in clinical randomized trials before implementation in the guidelines with a high level of evidence. [ABSTRACT FROM AUTHOR]

Aims: Iron deficiency (ID) is common in heart failure (HF) and linked with poor prognosis regardless of anaemia. We assessed temporal trends in ID testing, ID prevalence, ID incidence, iron need, and outcomes associated with ID in HF across the ejection fraction (EF) spectrum. Methods and results: From the Swedish HF registry, we enrolled 15 197 patients from Region Stockholm with available EF and collected laboratory tests from routine practice. Iron screening improved since 2016 but remained <25% as of 2018. In 1486 patients with iron biomarkers at baseline, the prevalence of ID was 55% (HF with reduced EF 54%; mildly reduced EF 51%; preserved EF 61%). Iron need was ≥1500 mg in 72% of patients. ID was independently associated with higher risk for HF rehospitalizations (incidence rate ratio [IRR] 1.62, 95% confidence interval [CI] 1.13–2.31) and with cardiovascular (CV) death or repeated HF hospitalizations (IRR 1.63, 95% CI 1.15–2.30) regardless of EF (p‐interaction 0.21 and 0.26, respectively), but not with all‐cause death, CV death, or first HF hospitalization. Among 96 patients without ID at baseline and with follow‐up iron biomarkers, 21% developed ID within 6 months. Conclusions: Iron deficiency screening improved over time but is still limitedly implemented, despite being highly prevalent and incident, and independently associated with CV death or HF rehospitalizations regardless of EF. Most patients with ID had an iron need necessitating either repeated administrations of intravenous iron or a preparation permitting >1000 mg doses. These data highlight the need for improved screening for ID in HF. [ABSTRACT FROM AUTHOR]

Background Individuals with chronic kidney disease (CKD) hospitalized with hyperkalemia are at risk of hyperkalemia recurrence and re-hospitalization. We present the rationale and design of CONTINUITY, a study to examine the efficacy of continuing sodium zirconium cyclosilicate (SZC)—an oral, highly selective potassium (K+) binder—compared with standard of care (SoC) on maintaining normokalemia and reducing re-hospitalization and resource utilization among participants with CKD hospitalized with hyperkalemia. Methods This Phase 4, randomized, open-label, multicenter study will enroll adults with Stage 3b–5 CKD and/or estimated glomerular filtration rate <45 mL/min/1.73 m2, within 3 months of eligibility screening, hospitalized with a serum potassium (sK+) level of >5.0–≤6.5 mmol/L, without ongoing K+ binder treatment. The study will include an in-hospital phase, where participants receive SZC for 2–21 days, and an outpatient (post-discharge) phase. At discharge, participants with sK+ 3.5–5.0 mmol/L will be randomized (1:1) to SZC or SoC and monitored for 180 days. The primary endpoint is the occurrence of normokalemia at 180 days. Secondary outcomes include incidence and number of hospital admissions or emergency department visits both with hyperkalemia as a contributing factor, and renin–angiotensin–aldosterone system inhibitor down-titration. The safety and tolerability of SZC will be evaluated. Ethics approval has been received from all relevant ethics committees. Enrollment started March 2022 and the estimated study end date is December 2023. Conclusions This study will assess the potential of SZC versus SoC in managing people with CKD and hyperkalemia post-discharge. Trial registration ClinicalTrials.gov identifier: NCT05347693; EudraCT: 2021-003527-14, registered on 19 October 2021. [ABSTRACT FROM AUTHOR]

Aims Left bundle branch block (LBBB) might be the first finding of cardiovascular diseases but also the prerequisite for cardiac resynchronization therapy (CRT) in heart failure (HF) with reduced ejection fraction (HFrEF). The prognosis for patients with LBBB and the implications of CRT in an unselected real-world setting are the focus of our study. Methods and results A central electrocardiogram (ECG) database and national registers have been screened to identify patients with LBBB. Predictors of HF and the use of CRT were identified with Cox models. The hazard ratios (HRs) of death, cardiovascular death (CVD), and HF hospitalization (HFH) were estimated according to CRT use. Of 5359 patients with LBBB and QRS > 150 ms, median age 76 years, 36% were female. At the time of index ECG, 41% had a previous history of HF and 27% developed HF. Among 1053 patients with a class I indication for CRT, only 60% received CRT with a median delay of 137 days, and it was associated with a lower risk of death [HR: 0.45, 95% confidence interval (CI): 0.36–0.57], CVD (HR: 0.47, 95% CI: 0.35–0.63), and HFH (HR: 0.56, 95% CI: 0.48–0.66). The age of over 75 years and the diagnosis of dementia and chronic obstructive pulmonary disease were predictors of CRT non-use, while having a pacing/defibrillator device independently predicted CRT use. Conclusion In an unselected LBBB population, CRT is underused but of great value for HF patients. Therefore, it is crucial to find ways of better implementing and understanding CRT utilization and characteristics that influence the management of our patients. [ABSTRACT FROM AUTHOR]

Aims: Heart failure (HF) with preserved ejection fraction (HFpEF) is associated with cardiovascular (CV) and non‐CV events, but long‐term risk is poorly studied. We assessed incidence and predictors of the long‐term CV and non‐CV events. Methods and results: Patients presenting with acute HF, EF ≥ 45%, and N‐terminal pro‐brain natriuretic peptide > 300 ng/L were enrolled in the Karolinska‐Rennes study in 2007–11 and were reassessed after 4–8 weeks in a stable state. Long‐term follow‐up was conducted in 2018. The Fine–Gray sub‐distribution hazard regression was used to detect predictors of CV and non‐CV deaths, investigated separately from baseline acute presentation (demographic data only) and from the 4–8 week outpatient visit (including echocardiographic data). Of 539 patients enrolled [median age 78 (interquartile range: 72–84) years; 52% female], 397 patients were available for the long‐term follow‐up. Over a median follow‐up time from acute presentation of 5.4 (2.1–7.9) years, 269 (68%) patients died, 128 (47%) from CV and 120 (45%) from non‐CV causes. Incidence rates per 1000 patient‐years were 62 [95% confidence interval (CI) 52–74] for CV and 58 (95% CI 48–69) for non‐CV death. Higher age and coronary artery disease (CAD) were independent predictors of CV death, and anaemia, stroke, kidney disease, and lower body mass index (BMI) and sodium concentrations of non‐CV death. From the stable 4–8 week visit, anaemia, CAD, and tricuspid regurgitation (>3.1 m/s) were independent predictors of CV death, and higher age of non‐CV death. Conclusions: In patients with acute decompensated HFpEF, over 5 years of follow‐up, nearly two‐thirds of patients died, half from CV and the other half from non‐CV causes. CAD and tricuspid regurgitation were associated with CV death. Stroke, kidney disease, lower BMI, and lower sodium were associated with non‐CV death. Anaemia and higher age were associated with both outcomes. [Correction added on 24 March 2023, after first online publication: In the first sentence of the Conclusions, 'two‐thirds' has been inserted before 'of patients died...' in this version.] [ABSTRACT FROM AUTHOR]