Search

Metabolic comorbidities are common in patients with cardiorenal disease; they can cause atherosclerotic cardiovascular disease (ASCVD), speed progression, and adversely affect prognosis. Common comorbidities are Type 2 diabetes mellitus (T2DM), obesity/overweight, chronic kidney disease (CKD), and chronic liver disease. The cardiovascular system, kidneys, and liver are linked to many of the same risk factors (e.g. dyslipidaemia, hypertension, tobacco use, diabetes, and central/truncal obesity), and shared metabolic and functional abnormalities lead to damage throughout these organs via overlapping pathophysiological pathways. The COVID-19 pandemic has further complicated the management of cardiometabolic diseases. Obesity, T2DM, CKD, and liver disease are associated with increased risk of poor outcomes of COVID-19 infection, and conversely, COVID-19 can lead to worsening of pre-existing ASCVD. The high rates of these comorbidities highlight the need to improve recognition and treatment of ASCVD in patients with obesity, insulin resistance or T2DM, chronic liver diseases, and CKD and equally, to improve recognition and treatment of these diseases in patients with ASCVD. Strategies to prevent and manage cardiometabolic diseases include lifestyle modification, pharmacotherapy, and surgery. There is a need for more programmes at the societal level to encourage a healthy diet and physical activity. Many pharmacotherapies offer mechanism-based approaches that can target multiple pathophysiological pathways across diseases. These include sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, selective mineralocorticoid receptor antagonists, and combined glucose-dependent insulinotropic peptide/glucagon-like peptide-1 receptor agonist. Non-surgical and surgical weight loss strategies can improve cardiometabolic disorders in individuals living with obesity. New biomarkers under investigation may help in the early identification of individuals at risk and reveal new treatment targets. [ABSTRACT FROM AUTHOR]

Background and Aims Ghrelin is an endogenous appetite-stimulating peptide hormone with potential cardiovascular benefits. Effects of acylated (activated) ghrelin were assessed in patients with heart failure and reduced ejection fraction (HFrEF) and in ex vivo mouse cardiomyocytes. Methods and results In a randomized placebo-controlled double-blind trial, 31 patients with chronic HFrEF were randomized to synthetic human acyl ghrelin (0.1 µg/kg/min) or placebo intravenously over 120 min. The primary outcome was change in cardiac output (CO). Isolated mouse cardiomyocytes were treated with acyl ghrelin and fractional shortening and calcium transients were assessed. Acyl ghrelin but not placebo increased cardiac output (acyl ghrelin: 4.08 ± 1.15 to 5.23 ± 1.98 L/min; placebo: 4.26 ± 1.23 to 4.11 ± 1.99 L/min, P < 0.001). Acyl ghrelin caused a significant increase in stroke volume and nominal increases in left ventricular ejection fraction and segmental longitudinal strain and tricuspid annular plane systolic excursion. There were no effects on blood pressure, arrhythmias, or ischaemia. Heart rate decreased nominally (acyl ghrelin: 71 ± 11 to 67 ± 11 b.p.m.; placebo 69 ± 8 to 68 ± 10 b.p.m.). In cardiomyocytes, acyl ghrelin increased fractional shortening, did not affect cellular Ca2+ transients, and reduced troponin I phosphorylation. The increase in fractional shortening and reduction in troponin I phosphorylation was blocked by the acyl ghrelin antagonist D-Lys 3. Conclusion In patients with HFrEF, acyl ghrelin increased cardiac output without causing hypotension, tachycardia, arrhythmia, or ischaemia. In isolated cardiomyocytes, acyl ghrelin increased contractility independently of preload and afterload and without Ca2+ mobilization, which may explain the lack of clinical side effects. Ghrelin treatment should be explored in additional randomized trials. Clinical Trial Registration ClinicalTrials.gov Identifier: NCT05277415 [ABSTRACT FROM AUTHOR]

Keywords: Randomized controlled trial; Clinical trial; Trial design; Registry; Heart failure; Reduced ejection fraction; Mildly reduced ejection fraction; Preserved ejection fraction; Outcomes; Mortality; Heart failure hospitalization EN Randomized controlled trial Clinical trial Trial design Registry Heart failure Reduced ejection fraction Mildly reduced ejection fraction Preserved ejection fraction Outcomes Mortality Heart failure hospitalization 1526 1529 4 05/03/23 20230501 NES 230501 Randomized controlled trials (RCTs) form the basis for guidelines, regulatory approval, and reimbursement.[1] They are commonly industry-funded and apply selective eligibility criteria,[2] potentially limiting generalizability. Real-world heart failure management in 10,910 patients with chronic heart failure in the Netherlands: design and rationale of the chronic heart failure ESC guideline-based cardiology practice quality project (CHECK-HF) registry. [Extracted from the article]

Heart Failure (HF) is a multi-faceted and life-threatening syndrome characterized by significant morbidity and mortality, poor functional capacity and quality of life, and high costs. HF affects more than 64 million people worldwide. Therefore, attempts to decrease its social and economic burden have become a major global public health priority. While the incidence of HF has stabilized and seems to be declining in industrialized countries, the prevalence is increasing due to the ageing of the population, improved treatment of and survival with ischaemic heart disease, and the availability of effective evidence-based therapies prolonging life in patients with HF. There are geographical variations in HF epidemiology. There is substantial lack of data from developing countries, where HF exhibits different features compared with that observed in the Western world. In this review, we provide a contemporary overview on the global burden of HF, providing updated estimates on prevalence, incidence, outcomes, and costs worldwide. [ABSTRACT FROM AUTHOR]

Aims To investigate the impact of patiromer on the serum potassium level and its ability to enable specified target doses of renin–angiotensin–aldosterone system inhibitor (RAASi) use in patients with heart failure and reduced ejection fraction (HFrEF). Methods and results A total of 1642 patients with HFrEF and current or a history of RAASi-related hyperkalemia were screened and 1195 were enrolled in the run-in phase with patiromer and optimization of the RAASi therapy [≥50% recommended dose of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, and 50 mg of mineralocorticoid receptor antagonist (MRA) spironolactone or eplerenone]. Specified target doses of the RAASi therapy were achieved in 878 (84.6%) patients; 439 were randomized to patiromer and 439 to placebo. All patients, physicians, and outcome assessors were blinded to treatment assignment. The primary endpoint was between-group difference in the adjusted mean change in serum potassium. Five hierarchical secondary endpoints were assessed. At the end of treatment, the median (interquartile range) duration of follow-up was 27 (13–43) weeks, the adjusted mean change in potassium was +0.03 mmol/l in the patiromer group and +0.13 mmol/l in the placebo group [difference in the adjusted mean change between patiromer and placebo: −0.10 mmol/l (95% confidence interval, CI −0.13, 0.07); P < 0.001]. Risk of hyperkalemia >5.5 mmol/l [hazard ratio (HR) 0.63; 95% CI 0.45, 0.87; P = 0.006), reduction of MRA dose (HR 0.62; 95% CI 0.45, 0.87; P = 0.006), and total adjusted hyperkalemia events/100 person-years (77.7 vs. 118.2; HR 0.66; 95% CI 0.53, 0.81; P < 0.001) were lower with patiromer. Hyperkalemia-related morbidity-adjusted events (win ratio 1.53, P < 0.001) and total RAASi use score (win ratio 1.25, P = 0.048) favored the patiromer arm. Adverse events were similar between groups. Conclusion Concurrent use of patiromer and high-dose MRAs reduces the risk of recurrent hyperkalemia (ClinicalTrials.gov: NCT03888066). [ABSTRACT FROM AUTHOR]

Aims This study aimed to investigate the incremental value offered by left atrial reservoir strain (LASr) to the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) diastolic algorithm to identify elevated left ventricular (LV) filling pressure in patients with preserved ejection fraction (EF). Methods and results Near-simultaneous echocardiography and right heart catheterization were performed in 210 patients with EF ≥50% in a large, dual-centre study. Elevated filling pressure was defined as invasive pulmonary capillary wedge pressure (PCWP) ≥15 mmHg. LASr was evaluated using speckle-tracking echocardiography. Diagnostic performance of the ASE/EACVI diastolic algorithm was validated against invasive reference and compared with modified algorithms incorporating LASr. Modest correlation was observed between E / e ′, E / A ratio, and LA volume index with PCWP (r = 0.46, 0.46, and 0.36, respectively; P < 0.001 for all). Mitral e ′ and TR peak velocity showed no association. The ASE/EACVI algorithm (89% feasibility, 71% sensitivity, 68% specificity) demonstrated reasonable ability (AUC = 0.69) and 68% accuracy to identify elevated LV filling pressure. LASr displayed strong ability to identify elevated PCWP (AUC = 0.76). Substituting TR peak velocity for LASr in the algorithm (69% sensitivity, 84% specificity) resulted in 91% feasibility, 81% accuracy, and stronger agreement with invasive measurements. Employing LASr as per expert consensus (71% sensitivity, 70% specificity) and adding LASr to conventional parameters (67% sensitivity, 84% specificity) also demonstrated greater feasibility (98% and 90%, respectively) and overall accuracy (70% and 80%, respectively) to estimate elevated PCWP. Conclusions LASr improves feasibility and overall accuracy of the ASE/EACVI algorithm to discern elevated filling pressures in patients with preserved EF. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is highly prevalent and associated with a two-fold increased mortality, mostly explained by cardiovascular diseases. Trial evidence on older glucose-lowering agents such as metformin and sulfonylureas is limited in terms of cardiovascular efficacy. Since 2008, after rosiglitazone was observed to increase the risk of myocardial infarction and heart failure (HF), cardiovascular outcome trials (CVOTs) have been required by regulators for licensing new glucose-lowering agents. In the following CVOTs, dipeptidyl peptidase 4 inhibitors (DPP4i) have been shown to be safe but not to improve mortality/morbidity, except for saxagliptin which increased the risk of HF. Several glucagon-like peptide-1 receptor agonists (GLP1-Ra) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been demonstrated to reduce the risk of cardiovascular mortality and morbidity. SGLT2i have shown a class effect for the reduction in risk of HF events in patients with T2DM, leading to trials testing their efficacy/safety in HF regardless of T2DM. In the DAPA-HF and the EMPEROR-Reduced trials dapagliflozin and empagliflozin, respectively, improved cardiovascular mortality/morbidity in patients with HF with reduced ejection fraction (HFrEF), with and without T2DM. Therefore, these drugs are now key part of HFrEF pharmacotherapy. In the SOLOIST-WHF, sotagliflozin reduced cardiovascular mortality/morbidity in patients with T2DM and a recent acute episode of HF regardless of ejection fraction (EF). In the EMPEROR-Preserved, empagliflozin reduced CV mortality/morbidity in patients with heart failure with mildly reduced (HFmrEF) and preserved (HFpEF) EF regardless of comorbid T2DM. The DELIVER is currently testing dapagliflozin in patients with HFmrEF and HFrEF. A strong renal protective role of SGLT2i has also emerged in trials enrolling patients with and without T2DM. [ABSTRACT FROM AUTHOR]

Standardized data definitions are essential for assessing the quality of care and patient outcomes in observational studies and randomized controlled trials. The European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart) project of the European Society of Cardiology (ESC) aims to create contemporary pan-European data standards for cardiovascular diseases, including heart failure (HF). We followed the EuroHeart methodology for cardiovascular data standard development. A Working Group including experts in HF registries, representatives from the Heart Failure Association of the ESC, and the EuroHeart was formed. Using Embase and Medline (2016–21), we conducted a systematic review of the literature on data standards, registries, and trials to identify variables pertinent to HF. A modified Delphi method was used to reach a consensus on the final set of variables. For each variable, the Working Group developed data definitions and agreed on whether it was mandatory (Level 1) or additional (Level 2). In total, 84 Level 1 and 79 Level 2 variables were selected for nine domains of HF care. These variables were reviewed by an international Reference Group with the Level 1 variables providing the dataset for registration of patients with HF on the EuroHeart IT platform. By means of a structured process and interaction with international stakeholders, harmonized data standards for HF have been developed. In the context of the EuroHeart, this will facilitate quality improvement, international observational research, registry-based randomized trials, and post-marketing surveillance of devices and pharmacotherapies across Europe. [ABSTRACT FROM AUTHOR]

The article presents the discussion on abnormal atrial structure and function termed as atrial myopathy or atrial disease being common in patients with heart failure (HF). Topics include atrial dilatation, fibrosis, and functional impairment being common if not universal accompaniments of both HF and AF; and containing collagen synthesis and degradation, autonomic innervation, activated platelets, and coagulation factors, and inflammatory pathways.

Aims: Randomized data on the efficacy/safety of cardiac resynchronization therapy with vs. without defibrillator (CRT-D,-P) in heart failure with reduced ejection fraction (HFrEF) are scarce. We aimed to evaluate survival associated with use of CRT-D vs. CRT-P in a contemporary cohort with HFrEF.Methods and Results: Patients from Swedish HF Registry treated with CRT-D/CRT-P and fulfilling criteria for primary prevention defibrillator use were included. Logistic regression was used to evaluate predictors of CRT-D non-use. All-cause mortality was compared in CRT-D vs. CRT-P by Cox regression in a 1 : 1 propensity-score-matched cohort. Of 1988 patients with CRT, 1108 (56%) had CRT-D and 880 (44%) CRT-P. Older age, higher ejection fraction (EF), female sex, and the lack of referral to HF nurse-led outpatient clinic were major determinants of CRT-D non-use. After matching, 645 CRT-D patients were compared with 645 with CRT-P. The CRT-D use was associated with lower 1- and 3-year all-cause mortality [hazard ratio (HR):0.76, 95% confidence interval (CI):0.58-0.98; HR: 0.82, 95% CI: 0.68-0.99, respectively]. Results were consistent in all pre-specified subgroups except for CRT-D use being associated with lower 3-year mortality in patients with an EF < 30% but not in those with an EF ≥ 30% (HR: 0.73, 95% CI: 0.59-0.89 and HR: 1.24, 95% CI: 0.83-1.85, respectively; P-interaction = 0.02).Conclusion: In a contemporary HFrEF cohort, CRT-D was associated with lower mortality compared with CRT-P. The CRT-D use was less likely in older patients, females, and in patients not referred to HF nurse-led outpatient clinic. Our findings support the use of CRT-D vs. CRT-P in HFrEF, in particular with severely reduced EF. [ABSTRACT FROM AUTHOR]

The prognosis of HF has improved over time, but mortality remains high.[1] In the European Society of Cardiology (ESC) HF-Longterm (LT) registry, 1-year mortality was 23.6% for acute HF and 6.4% for chronic HF in 21 European countries between 2011 and 2013.[8] Another analysis from the ESC-HF-LT registry including 9,134 ambulatory HF patients showed that 1-year mortality was highest in HFrEF (8.8%), followed by HFmrEF (7.6%) and HFpEF (6.3%).[1] Between 2005 and 2009 in the United Satates, the median survival of patients admitted with worsening HF was 2.1 years, and 5-year mortality was 75.4%, with a comparable 5-year mortality in patients with HFrEF vs. Heart failure (HF) is a heterogenous and life-threatening syndrome that affects more than 60 million individuals globally and is characterised by severe morbidity and mortality, poor quality of life, and a high burden on the healthcare systems in terms of resource use and expenditures.[1] The 2019 Heart Failure Association (HFA) ATLAS provided estimates concerning important aspects of HF epidemiology in Europe and reported a HF prevalence ranging from <=12 in Spain and Greece to over >30 per 1000 persons in Lithuania and Germany.[2] The prevalence of HF in the United States was estimated at 2.4% in 2012.[1] Prevalence estimates in Asia range between 1.3% and 6.7%.[1] Notably, the prevalence of HF is further projected to increase worldwide due to the aging of populations, improved treatments for ischaemic heart disease, and the availibility of effective evidence-based therapies prolonging life in patients with established HF, most notably HF with reduced ejection fraction (HFrEF).[1] Data on the prevalence of the different HF phenotypes stratified by EF [HFrEF, HF with mildly reduced ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF)] are limited due to the lack of an ejection fraction (EF) assessment in numerous large-scale registries and administrative datasets. [Extracted from the article]

Aims Patients with heart failure and preserved ejection fraction (HFpEF) frequently have difficult-to-control hypertension. We examined the effect of neprilysin inhibition on 'apparent resistant hypertension' in patients with HFpEF in the PARAGON-HF trial, which compared the effect of sacubitril–valsartan with valsartan. Methods and results In this post hoc analysis, patients were categorized according to systolic blood pressure at the end of the valsartan run-in (n  = 4795). 'Apparent resistant hypertension' was defined as systolic blood pressure ≥140 mmHg (≥135 mmHg if diabetes) despite treatment with valsartan, a calcium channel blocker, and a diuretic. 'Apparent mineralocorticoid receptor antagonist (MRA)-resistant' hypertension was defined as systolic blood pressure ≥140 mmHg (≥135 mmHg if diabetes) despite the above treatments and an MRA. The primary outcome in the PARAGON-HF trial was a composite of total hospitalizations for heart failure and death from cardiovascular causes. We examined clinical endpoints and the safety of sacubitril–valsartan according to the hypertension category. We also examined reductions in blood pressure from the end of valsartan run-in to Weeks 4 and 16 after randomization. Overall, 731 patients (15.2%) had apparent resistant hypertension and 135 (2.8%) had apparent MRA-resistant hypertension. The rate of the primary outcome was higher in patients with apparent resistant hypertension [17.3; 95% confidence interval (CI) 15.6–19.1 per 100 person-years] compared to those with a controlled systolic blood pressure (13.4; 12.7–14.3 per 100 person-years), with an adjusted rate ratio of 1.28 (95% CI 1.05–1.57). The reduction in systolic blood pressure at Weeks 4 and 16, respectively, was greater with sacubitril–valsartan vs. valsartan in patients with apparent resistant hypertension [−4.8 (−7.0 to −2.5) and 3.9 (−6.6 to −1.3) mmHg] and apparent MRA-resistant hypertension [−8.8 (−14.0 to −3.5) and −6.3 (−12.5 to −0.1) mmHg]. The proportion of patients with apparent resistant hypertension achieving a controlled systolic blood pressure by Week 16 was 47.9% in the sacubitril–valsartan group and 34.3% in the valsartan group [adjusted odds ratio (OR) 1.78, 95% CI 1.30–2.43]. In patients with apparent MRA-resistant hypertension, the respective proportions were 43.6% vs. 28.4% (adjusted OR 2.63, 95% CI 1.18–5.89). Conclusion Sacubitril–valsartan may be useful in treating apparent resistant hypertension in patients with HFpEF, even in those who continue to have an elevated blood pressure despite treatment with at least four antihypertensive drug classes, including an MRA. Clinical trial registration PARAGON-HF: ClinicalTrials.gov Identifier NCT01920711. [ABSTRACT FROM AUTHOR]

Cardiac resynchronization therapy (CRT) is one of the most effective therapies for heart failure with reduced ejection fraction and leads to improved quality of life, reductions in heart failure hospitalization rates and all-cause mortality. Nevertheless, up to two-thirds of eligible patients are not referred for CRT. Furthermore, post-implantation follow-up is often fragmented and suboptimal, hampering the potential maximal treatment effect. This joint position statement from three European Society of Cardiology Associations, Heart Failure Association (HFA), European Heart Rhythm Association (EHRA) and European Association of Cardiovascular Imaging (EACVI), focuses on optimized implementation of CRT. We offer theoretical and practical strategies to achieve more comprehensive CRT referral and post-procedural care by focusing on four actionable domains: (i) overcoming CRT under-utilization, (ii) better understanding of pre-implant characteristics, (iii) abandoning the term 'non-response' and replacing this by the concept of disease modification, and (iv) implementing a dedicated post-implant CRT care pathway. [ABSTRACT FROM AUTHOR]

Secondary (or functional) mitral regurgitation (SMR) occurs frequently in chronic heart failure (HF) with reduced left ventricular (LV) ejection fraction, resulting from LV remodelling that prevents coaptation of the valve leaflets. Secondary mitral regurgitation contributes to progression of the symptoms and signs of HF and confers worse prognosis. The management of HF patients with SMR is complex and requires timely referral to a multidisciplinary Heart Team. Optimization of pharmacological and device therapy according to guideline recommendations is crucial. Further management requires careful clinical and imaging assessment, addressing the anatomical and functional features of the mitral valve and left ventricle, overall HF status, and relevant comorbidities. Evidence concerning surgical correction of SMR is sparse and it is doubtful whether this approach improves prognosis. Transcatheter repair has emerged as a promising alternative, but the conflicting results of current randomized trials require careful interpretation. This collaborative position statement, developed by four key associations of the European Society of Cardiology—the Heart Failure Association (HFA), European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Association of Cardiovascular Imaging (EACVI), and European Heart Rhythm Association (EHRA)—presents an updated practical approach to the evaluation and management of patients with HF and SMR based upon a Heart Team approach. [ABSTRACT FROM AUTHOR]

Background In patients with severe left ventricular dysfunction, recurrent ventricular tachycardia (VT) non-responsive to antiarrhythmic therapies may cause further deterioration of cardiac function and haemodynamic instability. The use of extracorporeal membrane oxygenation (ECMO) in the setting of haemodynamically unstable VT may allow rhythm stabilization and can be effective in providing haemodynamic stability during VT ablation procedures. Case summary We describe the clinical course of a patient with ischaemic cardiomyopathy and recurrent VTs in the early post-myocardial infarction (MI) period. Nineteen days after MI, the patient started to experience recurrent attacks of VT, which became more frequent and non-responsive to medical treatment including amiodarone and lidocaine. The patient developed cardiogenic shock and a decision was made to institute ECMO. The patient was supported with ECMO for 32 days because of heart failure, refractory VT, and recurrent infections. An electrophysiological study was performed 4 days after ECMO initiation, which revealed a large scar area in the left ventricle. Radiofrequency energy was applied 69 times, rendering the VT non-inducible. Subsequently, VT attacks disappeared and the patient was weaned from ECMO after 32 days. The patient received a left ventricular assist device 5 days post-ECMO weaning and was then transplanted. Discussion There is still no evidence or guidelines regarding patients with refractory VT; however, ECMO support has been successfully used during VT ablation procedures. In this case report, VT ablation had a crucial role in treating the culprit arrhythmia while the implementation of ECMO allowed a complex ablation procedure to be completed safely. [ABSTRACT FROM AUTHOR]

An editorial is presented on Primary care heart failure service identifying a missed cohort of heart failure patients with reduced ejection fraction. Topics include receiving renin–angiotensin–aldosterone system inhibitors (RAASi) or angiotensin receptor neprilysin inhibitor (ARNi) or ivabradine; and lacking suitable sources for systematic screening such as electronic medical records, diagnostic coding, and medication prescriptions and use.

Recurrent hyperkalaemia management and use of renin-angiotensin-aldosterone system inhibitors: a European multi-national targeted chart review. [Extracted from the article]

Aims: To evaluate population-based electronic health record (EHR) definitions of atrial fibrillation (AF) and valvular heart disease (VHD) subtypes, time trends in prevalence and prognosis.Methods and Results: A total of 76 019 individuals with AF were identified in England in 1998-2010 in the CALIBER resource, linking primary and secondary care EHR. An algorithm was created, implemented, and refined to identify 18 VHD subtypes using 406 diagnosis, procedure, and prescription codes. Cox models were used to investigate associations with a composite endpoint of incident stroke (ischaemic, haemorrhagic, and unspecified), systemic embolism (SSE), and all-cause mortality. Among individuals with AF, the prevalence of AF with concomitant VHD increased from 11.4% (527/4613) in 1998 to 17.6% (7014/39 868) in 2010 and also in individuals aged over 65 years. Those with mechanical valves, mitral stenosis (MS), or aortic stenosis had highest risk of clinical events compared to AF patients with no VHD, in relative [hazard ratio (95% confidence interval): 1.13 (1.02-1.24), 1.20 (1.05-1.36), and 1.27 (1.19-1.37), respectively] and absolute (excess risk: 2.04, 4.20, and 6.37 per 100 person-years, respectively) terms. Of the 95.2% of individuals with indication for warfarin (men and women with CHA2DS2-VASc ≥1 and ≥2, respectively), only 21.8% had a prescription 90 days prior to the study.Conclusion: Prevalence of VHD among individuals with AF increased from 1998 to 2010. Atrial fibrillation associated with aortic stenosis, MS, or mechanical valves (compared to AF without VHD) was associated with an excess absolute risk of stroke, SSE, and mortality, but anticoagulation was underused in the pre-direct oral anticoagulant (DOAC) era, highlighting need for urgent clarity regarding DOACs in AF and concomitant VHD. [ABSTRACT FROM AUTHOR]

Background Small-scale studies suggest that hyperkalaemia is a less threatening condition in chronic kidney disease (CKD), arguing adaptation/tolerance to potassium (K+) retention. This study formally evaluates this hypothesis by estimating the distribution of plasma K+ and its association with mortality across CKD stages. Methods This observational study included all patients undergoing plasma K+ testing in Stockholm during 2006–11. We randomly selected one K+ measurement per patient and constructed a cross-sectional cohort with mortality follow-up. Covariates included demographics, comorbidities, medications and estimated glomerular filtration rate (eGFR). We estimated K+ distribution and defined K+ ranges associated with 90-, 180- and 365-day mortality. Results Included were 831 760 participants, of which 70 403 (8.5%) had CKD G3 (eGFR <60–30 mL/min) and 8594 (1.1%) had CKD G4–G5 (eGFR <30 mL/min). About 66 317 deaths occurred within a year. Adjusted plasma K+ increased across worse CKD stages: from median 3.98 (95% confidence interval 3.49–4.59) for eGFR >90 to 4.43 (3.22–5.65) mmol/L for eGFR ≤15 mL/min/1.73 m2. The association between K+ and mortality was U-shaped, but it flattened at lower eGFR strata and shifted upwards. For instance, the range where the 90-day mortality risk increased by no more than 100% was 3.45–4.94 mmol/L in eGFR >60 mL/min, but was 3.36–5.18  in G3 and 3.26–5.53 mmol/L in G4–G5. In conclusion, CKD stage modifies K+ distribution and the ranges that predict mortality in the community. Conclusion Although this study supports the view that hyperkalaemia is better tolerated with worse CKD, it challenges the current use of a single optimal K+ range for all patients. [ABSTRACT FROM AUTHOR]

Long-term mechanical circulatory support (LT-MCS) is an important treatment modality for patients with severe heart failure. Different devices are available, and many—sometimes contradictory—observations regarding patient selection, surgical techniques, perioperative management and follow-up have been published. With the growing expertise in this field, the European Association for Cardio-Thoracic Surgery (EACTS) recognized a need for a structured multidisciplinary consensus about the approach to patients with LT-MCS. However, the evidence published so far is insufficient to allow for generation of meaningful guidelines complying with EACTS requirements. Instead, the EACTS presents an expert opinion in the LT-MCS field. This expert opinion addresses patient evaluation and preoperative optimization as well as management of cardiac and non-cardiac comorbidities. Further, extensive operative implantation techniques are summarized and evaluated by leading experts, depending on both patient characteristics and device selection. The faculty recognized that postoperative management is multidisciplinary and includes aspects of intensive care unit stay, rehabilitation, ambulatory care, myocardial recovery and end-of-life care and mirrored this fact in this paper. Additionally, the opinions of experts on diagnosis and management of adverse events including bleeding, cerebrovascular accidents and device malfunction are presented. In this expert consensus, the evidence for the complete management from patient selection to end-of-life care is carefully reviewed with the aim of guiding clinicians in optimizing management of patients considered for or supported by an LT-MCS device. [ABSTRACT FROM AUTHOR]

Aim To investigate the characteristics long-term prognostic implications (up to ∼2.2 years) of atrial fibrillation (AF) compared to sinus rhythm (SR), between acute and chronic heart failure (HF) with reduced (HFrEF < 40%), mid-range (HFmrEF 40–49%), and preserved (HFpEF ≥ 50%) ejection fraction (EF). Methods and results Data from the observational, prospective, HF long-term registry of the European Society of Cardiology were analysed. A total of 14 964 HF patients (age 66 ± 13 years, 67% male; 53% HFrEF, 21% HFmrEF, 26% HFpEF) were enrolled. The prevalence of AF was 27% in HFrEF, 29% in HFmrEF, and 39% in HFpEF. Atrial fibrillation was associated with older age, lower functional capacity, and heightened physical signs of HF. Crude rates of mortality and HF hospitalization were higher in patients with AF compared to SR, in each EF subtype. After multivariable adjustment, the hazard ratio of AF for HF hospitalizations was: 1.036 (95% CI 0.888–1.208, P  =   0.652) in HFrEF, 1.430 (95% CI 1.087–1.882, P  =   0.011) in HFmrEF, and 1.487 (95% CI 1.195–1.851, P  <   0.001) in HFpEF; and for combined all-cause death or HF hospitalizations: 0.957 (95% CI 0.843–1.087, P  =   0.502), 1.302 (95% CI 1.055–1.608, P  =   0.014), and 1.365 (95% CI 1.152–1.619, P  <   0.001), respectively. In patients with HFrEF, AF was not associated with worse outcomes in those presenting with either an acute or a chronic presentation of HF. Conclusions The prevalence of AF increases with increasing EF but its association with worse cardiovascular outcomes, remained significant in patients with HFpEF and HFmrEF, but not in those with HFrEF. [ABSTRACT FROM AUTHOR]

Aims In heart failure with reduced ejection fraction (HFrEF), renin–angiotensin system inhibitors (RASi) improve morbidity and mortality. However, patients aged >80 years constituted a small minority in trials. We assessed the association between RASi use and mortality/morbidity in HFrEF patients aged >80 years. Methods and results We included patients with ejection fraction <40% and age >80 years from the Swedish Heart Failure Registry. Propensity scores for RASi use were calculated from 37 variables. Cox regression models for RASi vs. non-RASi with all-cause mortality and all-cause mortality/heart failure (HF) hospitalization as outcomes were fitted in a 1:1 propensity-score-matched cohort. To assess consistency, the same analyses were performed in a 'positive control' cohort aged ≤80 years. Of 6710 patients [median age (interquartile range) 85 (82–87) years; 38% women], 5384 (80%) received RASi. Propensity-score matching yielded 2416 patients, [age 86 (83–91) years]. RASi use was associated with hazard ratio (HR) (95% confidence interval) 0.78 (0.72–0.86) for all-cause mortality and 0.86 (0.79–0.94) for all-cause mortality/HF hospitalization. In positive control patients aged ≤80 years (17 842 patients in the overall cohort, 2126 after matching), HR for all-cause mortality was 0.81 (0.71–0.91), whereas it was 0.85 (0.76–0.94) for all-cause mortality/HF hospitalization. Conclusion In HFrEF patients with age >80 years, RASi were relatively underused compared with in younger patients, despite similar association with reduced morbidity and mortality and no apparent association with risk of syncope-related hospitalization. These results may be interpreted as hypothesis generating for randomized clinical trials on RASi in this elderly HFrEF subpopulation. View large Download slide View large Download slide [ABSTRACT FROM AUTHOR]

Aims: Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome with various phenotypes and outcomes. The prognostic relevance of echocardiography and the E/e' ratio has previously been reported. We sought to study in addition, the value of estimated pulmonary pressure and left atrial size for diagnosing and determining a prognosis for HFpEF-patients in a prospective multi-centric cohort. Methods and results: Patients with an acute-HF event accompanied with NT-proBNP >300 pg/mL (BNP > 00 pg/mL) and LVEF >45% were included (n = 237) and clinically reassessed using echo-Doppler after 4-8 weeks of HF treatment as part of the prospective KaRen HFpEF study. A core-centre performed the echocardiographic analyses. A combined primary endpoint of either HF hospitalizations and mortality over a span of 18-month, or simply mortality (secondary endpoint) were used. The mean LVEF was 62 ± 7%, E/e':12.9 ± 6.0, left atrial volume index (LAVI): 48.1 ± 15.9 ml/m², TR: 2.9 ± 0.9 m/s. Patients with both LAVI > 40 ml/m² and TR > 3.1 m/s had a significantly greater risk of death or heart failure related hospitalization than others (P = 0.014 after adjustment). Conclusion: The combination of enlarged LA and elevated estimated pulmonary pressure has a strong prognostic impact in patients suffering from HFpEF. Our results indicate that such patients constitute a risk group in HFpEF which requires dedicated medical attention. ClinicalTrials.gov: NCT00774709. [ABSTRACT FROM AUTHOR]

BACKGROUND: KaRen is a multicentre study designed to characterize and follow patients with heart failure and preserved ejection fraction (HFpEF). In a subgroup of patients with clinical signs of congestion but left ventricular ejection fraction (LVEF) >45%, we sought to describe and analyse the potential prognostic value of echocardiographic parameters recorded not only at rest but also during a submaximal exercise stress echocardiography. Exercise-induced changes in echo parameters might improve our ability to characterize HFpEF patients. METHOD AND RESULTS: Patients were prospectively recruited in a single tertiary centre following an acute HF episode with NT-pro-BNP >300 pg/mL (BNP > 100 pg/mL) and LVEF > 45% and reassessed by exercise echo-Doppler after 4-8 weeks of dedicated treatment. Image acquisitions were standardized, and analysis made at end of follow-up blinded to patients' clinical status and outcome. In total, 60 patients having standardized echocardiographic acquisitions were included in the analysis. Twenty-six patients (43%) died or were hospitalized for HF (primary outcome). The mean ± SD workload was 45 ± 14 watts (W). Mean ± SD resting LVEF and LV global longitudinal strain was 57.6 ± 9.5% and -14.5 ± 4.2%, respectively. Mean ± SD resting E/e' was 11.3 ± 4.7 and 13.1 ± 5.3 in those patients who did not and those who did experience the primary outcome, respectively (P = 0.03). Tricuspid regurgitation (TR) peak velocity during exercise were 3.3 ± 0.5 and 3.7 ± 0.5 m/s (P = 0.01). Exercise TR was independently associated with HF-hospitalization or death after adjustment on baseline clinical and biological characteristics. CONCLUSION: Exercise echocardiography may contribute to identify HFpEF patients and especially high-risk ones. Our study suggested a prognostic value of TR recorded during an exercise. That was demonstrated independently of the value of resting E/e'. [ABSTRACT FROM AUTHOR]

Aims In heart failure (HF) with reduced ejection fraction (EF), renin-angiotensin receptor (RAS) antagonists reduce mortality. However, severe renal insufficiency was an exclusion criterion in trials. We tested the hypothesis that RAS antagonists are associated with reduced mortality also in HF with severe renal insufficiency. Methods and results We studied patientswith EF ≤39%registered in the prospective Swedish Heart Failure Registry. In patientswith creatinine >221 μmol/L or creatinine clearance <30 mL/min, propensity scores for RAS-antagonist usewere derived from 36 variables. The association between RAS antagonist use and all-cause mortality was assessed with Cox regression in a cohort matched 1:1 based on age and propensity score. To assess consistency, we performed the same analysis as a 'positive control' in patients without severe renal insufficiency. Between 2000 and 2013, there were 24 283 patients of which 2410 [age, mean (SD), 82 (9), 45% women] had creatinine .221 mmol/L or creatinine clearance <30 mL/min and were treated (n = 1602) or not treated (n = 808) with RAS antagonists. In the matched cohort of 602 vs. 602 patients [age 83 (8), 42%women], RAS antagonist usewas associatedwith 55%[95%confidence interval (CI) 51-59] vs. 45%(41- 49) 1-year survival, P<0.001, with a hazard ratio (HR) for mortality of 0.76 (95% CI 0.67-0.86, P<0.001). In positive control patients without severe renal insufficiency [n = 21 873; age 71 (12), 27% women], thematched HRwas 0.79 (95% CI 0.72-0.86, P < 0.001). Conclusion In HF with severe renal insufficiency, the use of RAS antagonists was associated with lower all-cause mortality. Prospective randomized trials are needed before these findings can be applied to clinical practice. [ABSTRACT FROM AUTHOR]

Aims It has been suggested that cardiac resynchronization therapy (CRT) is less utilized, dyssynchrony occurs at narrower QRS, and CRT is more beneficial in women compared with men. We tested the hypotheses that (i) CRT is more underutilized and (ii) QRS prolongation and left bundle branch block (LBBB) are more harmful in women. Methods and results We studied 14 713 patients (28% women) with left ventricular ejection fraction (LVEF) <40% in the Swedish Heart Failure Registry. In women vs. men, CRT was present in 4 vs. 7% (P < 0.001) and was absent but with indication in 30 vs. 31% (P = 0.826). Next, among 13 782 patients (28% women) without CRT, 9% of women and 17% of men had non-specific intraventricular conduction delay (IVCD) and 27% of women and 24% of men had LBBB. One-year survival with narrow QRS was 85% in women and 88% in men, with IVCD 74 and 78%, and with LBBB 84 and 82%, respectively. Compared with narrow QRS, IVCD had a multivariable hazard ratio of 1.24 (95% CI 1.05–1.46, P = 0.011) in women and 1.30 (95% CI 1.19–1.42, P < 0.001) in men, and LBBB 1.03 (95% CI 0.91–1.16, P = 0.651) in women and 1.16 (95% CI 1.07–1.26, P < 0.001) in men, P for interaction between gender and QRS morphology, 0.241. Conclusions While the proportion with CRT was lower in women, CRT was equally underutilized in both genders. QRS prolongation with or without LBBB was not more harmful in women than in men. Efforts to improve CRT implementation should be directed equally towards women and men. [ABSTRACT FROM PUBLISHER]

Aims Cardiac resynchronization therapy (CRT) and primary prophylactic implantable cardioverter-defibrillators (ICDs) are underutilized in heart failure (HF). This may originate from an unawareness of device benefits and indications among physicians responsible for HF care and referral. We aimed to describe the awareness of indications for device therapy in a generalized sample of Swedish physicians. Methods and results A randomly selected sample of Swedish physicians specializing in cardiology, internal medicine, and family medicine and interns (5% of eligible physicians, n = 519) was invited to fill in a 23-item survey, testing their awareness of indications for device therapy and, as comparison, pharmacological therapy. Acceptable awareness (AA) of CRT indication was predefined as recognizing that a left bundle branch block on ECG warrants further evaluation for CRT. Acceptable awareness of ICD indication was predefined as recognizing that ejection fraction ≤35% alone, without a history of ventricular tachycardia, is sufficient to warrant a primary prophylactic ICD. The response rate was 37% (n = 168). Overall, 32% met AA of CRT indication, and significantly less (15%) met AA of ICD indication. Specialist certification in cardiology was the only significant predictor for AA [odds ratio (95% confidence interval): 37 (10–138)]. However, even among cardiologists, awareness of ICD indications was low (61% with AA). Guideline-recommended indications for pharmacological therapy were conceived significantly better (P = 0.02) than device therapy [median (interquartile range) of correct answers: 50% (33–50) compared with 36% (14–57)]. Conclusions The study identified an important and substantial awareness gap in the medical community that may explain some of the previously reported low referral rates and utilization of device therapy in HF. [ABSTRACT FROM PUBLISHER]

Aims The independent clinical correlates and prognostic impact of QRS prolongation in heart failure (HF) with reduced and preserved ejection fraction (EF) are poorly understood. The rationale for cardiac resynchronization therapy (CRT) in preserved EF is unknown. The aim was to determine the prevalence of, correlates with, and prognostic impact of QRS prolongation in HF with reduced and preserved EF. Methods and results We studied 25 171 patients (age 74.6 ± 12.0 years, 39.9% women) in the Swedish Heart Failure Registry. We assessed QRS width and 40 other clinically relevant variables. Correlates with QRS width were assessed with multivariable logistic regression, and the association between QRS width and all-cause mortality with multivariable Cox regression. Pre-specified subgroup analyses by EF were performed. Thirty-one per cent had QRS ≥120 ms. Strong predictors of QRS ≥120 ms were higher age, male gender, dilated cardiomyopathy, longer duration of HF, and lower EF. One-year survival was 77% in QRS ≥120 vs. 82% in QRS <120 ms, and 5-year survival was 42 vs. 51%, respectively (P < 0.001). The adjusted hazard ratio for all-cause mortality was 1.11 (95% confidence interval 1.04–1.18, P = 0.001) for QRS ≥120 vs. <120 ms. There was no interaction between QRS width and EF. Conclusion QRS prolongation is associated with other markers of severity in HF but is also an independent risk factor for all-cause mortality. The risk associated with QRS prolongation may be similar regardless of EF. This provides a rationale for trials of CRT in HF with preserved EF. [ABSTRACT FROM PUBLISHER]

Aims Cardiac resynchronization therapy (CRT) improves prognosis in patients with moderate-to-severe heart failure, reduced left ventricular ejection fraction, and wide QRS complexes. However, CRT may be under-utilized in women and data on long-term follow-up are still scarce. The aim was to investigate long-term mortality and hospitalization and prognostic impact of gender after CRT. Methods and results Data on 619 consecutive patients (19% women) that received CRT at a single centre between 1998 and 2008 were collected from electronic medical records and national death and hospitalization registries up to 2010. The primary endpoint was death of any cause and the secondary endpoint was combined death of any cause or heart failure hospitalization. Over a mean follow-up of 1320 ± 786 days, 215 (35%) patients reached the primary endpoint and 437 (71%) the secondary endpoint. Overall, 1-, 5-, and 10-year survivals were 91, 63, and 39%, respectively. Female gender was the only independent predictor of all-cause mortality; hazard ratio (HR) 0.44 [95% confidence interval (CI), 0.21–0.90; P= 0.025]. Women also had a trend towards lower risk for the secondary endpoint, HR 0.68 (95% CI, 0.45–1.04; P= 0.072). Conclusion In this registry analysis, patients with CRT had similarly high short-term survival to those in controlled trials, and this favourable prognosis was sustained over the long term.Women had lower all-cause mortality than men. [ABSTRACT FROM PUBLISHER]