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1.
  • Aktaa, Suleman, et al. (författare)
  • European Society of Cardiology Quality Indicators for the care and outcomes of cardiac pacing : developed by the Working Group for Cardiac Pacing Quality Indicators in collaboration with the European Heart Rhythm Association of the European Society of Cardiology
  • 2022
  • Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 24:1, s. 165-172
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: To develop a suite of quality indicators (QIs) for the evaluation of the care and outcomes for adults undergoing cardiac pacing.METHODS AND RESULTS: Under the auspice of the Clinical Practice Guideline Quality Indicator Committee of the European Society of Cardiology (ESC), the Working Group for cardiac pacing QIs was formed. The Group comprised Task Force members of the 2021 ESC Clinical Practice Guidelines on Cardiac Pacing and Cardiac Resynchronization Therapy, members of the European Heart Rhythm Association, international cardiac device experts, and patient representatives. We followed the ESC methodology for QI development, which involved (i) the identification of the key domains of care by constructing a conceptual framework of the management of patients receiving cardiac pacing, (ii) the development of candidate QIs by conducting a systematic review of the literature, (iii) the selection of the final set of QIs using a modified-Delphi method, and (iv) the evaluation of the feasibility of the developed QIs. Four domains of care were identified: (i) structural framework, (ii) patient assessment, (iii) pacing strategy, and (iv) clinical outcomes. In total, seven main and four secondary QIs were selected across these domains and were embedded within the 2021 ESC Guidelines on Cardiac Pacing and Cardiac Resynchronization therapy.CONCLUSION: By way of a standardized process, 11 QIs for cardiac pacing were developed. These indicators may be used to quantify adherence to guideline-recommended clinical practice and have the potential to improve the care and outcomes of patients receiving cardiac pacemakers.
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  • Asp, Michaela, et al. (författare)
  • Spatial detection of fetal marker genes expressed at low level in adult human heart tissue
  • 2017
  • Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Heart failure is a major health problem linked to poor quality of life and high mortality rates. Hence, novel biomarkers, such as fetal marker genes with low expression levels, could potentially differentiate disease states in order to improve therapy. In many studies on heart failure, cardiac biopsies have been analyzed as uniform pieces of tissue with bulk techniques, but this homogenization approach can mask medically relevant phenotypes occurring only in isolated parts of the tissue. This study examines such spatial variations within and between regions of cardiac biopsies. In contrast to standard RNA sequencing, this approach provides a spatially resolved transcriptome- and tissue-wide perspective of the adult human heart, and enables detection of fetal marker genes expressed by minor subpopulations of cells within the tissue. Analysis of patients with heart failure, with preserved ejection fraction, demonstrated spatially divergent expression of fetal genes in cardiac biopsies.
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  • Auricchio, Angelo, et al. (författare)
  • Sex-Related Procedural Aspects and Complications in CRT Survey II : A Multicenter European Experience in 11,088 Patients
  • 2019
  • Ingår i: JACC. - : Elsevier BV. - 2405-500X .- 2405-5018. ; 5:9, s. 1048-1058
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: This study sought to compare sex difference for procedural aspects and complications in the European Society of Cardiology CRT Survey II, exploring whether adverse events were related to the type of CRT device implanted.BACKGROUND: Sex-related differences in procedural aspects and complications in patients undergoing cardiac resynchronization therapy (CRT) implantation has not been explored in a real-life population.METHODS: A post-hoc analysis of procedural data and complications in different sexes and factors associated with events was performed from data collected in the European Society of Cardiology CRT Survey II.RESULTS: Of all patients (n = 11,088) included, 24.3% were women. The mean age (70 years of age) of male and female recipients was similar. Female patients more frequently had an idiopathic cardiomyopathy (67.4% vs. 44.1%) and fewer comorbidities, including atrial fibrillation (34.8% vs. 42.8%), diabetes (29.1% vs. 32.1%), chronic obstructive lung disease (10.3% vs. 12.6%), and renal failure (28.7% vs. 31.9%), compared with men. More women compared with men had a pacemaker (56.6% vs. 46.3%) and much less often an implantable cardioverter-defibrillator (CRT-D) (19.0% vs. 34.7%) implant. Periprocedural event rate was the highest in women with CRT with defibrillator (7.1% vs. 4.8% in men), followed by women with a CRT with pacing (5.5% vs. 4.4% in men). The higher periprocedural event rate in CRT-D women was attributable primarily to the occurrence of pneumothorax (1.4%), coronary sinus dissection (2.1%), and pericardial tamponade (0.3%). The rate of in-hospital major adverse events (6.0%) and complications necessitating reoperation (4.0%) was not different among sex and device type.CONCLUSIONS: Women are more likely to experience adverse procedure-related events during CRT implantation. Thus, preventive strategies should be employed to minimize complication rate.
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  • Bakhai, Ameet, et al. (författare)
  • Development of a health economic model to evaluate the potential benefits of optimal serum potassium management in patients with heart failure.
  • 2018
  • Ingår i: Journal of Medical Economics. - : Informa UK Limited. - 1369-6998 .- 1941-837X. ; 21:12, s. 1172-1182
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Patients with heart failure are at increased risk of hyperkalemia, particularly when treated with renin-angiotensin-aldosterone system inhibitor (RAASi) agents. This study developed a model to quantify the potential health and economic value associated with sustained potassium management and optimal RAASi therapy in heart failure patients.Materials and methods: A patient-level, fixed-time increment stochastic simulation model was designed to characterize the progression of heart failure through New York Heart Association functional classes, and predict associations between serum potassium levels, RAASi use, and consequent long-term outcomes. Following internal and external validation exercises, model analyses sought to quantify the health and economic benefits of optimizing both serum potassium levels and RAASi therapy in heart failure patients. Analyses were conducted using a UK payer perspective, independent of costs and utilities related to pharmacological potassium management.Results: Validation against multiple datasets demonstrated the predictive capability of the model. Compared to those who discontinued RAASi to manage serum potassium, patients with normokalemia and ongoing RAASi therapy benefited from longer life expectancy (+1.38 years), per-patient quality-adjusted life year gains (+0.53 QALYs), cost savings (110) pound, and associated net monetary benefit (10,679 pound at 20,000 pound per QALY gained) over a lifetime horizon. The predicted value of sustained potassium management and ongoing RAASi treatment was largely driven by reduced mortality and hospitalization risks associated with optimal RAASi therapy.Limitations: Several modeling assumptions were made to account for a current paucity of published literature; however, ongoing refinement and validation of the model will ensure its continued accuracy as the clinical landscape of hyperkalemia evolves.Conclusions: Predictions generated by this novel modeling approach highlight the value of sustained potassium management to avoid hyperkalemia, enable RAASi therapy, and improve long-term health economic outcomes in patients with heart failure.
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  • Braunschweig, Frieder, et al. (författare)
  • New York Heart Association functional class, QRS duration, and survival in heart failure with reduced ejection fraction : implications for cardiac resychronization therapy.
  • 2017
  • Ingår i: European Journal of Heart Failure. - : Wiley-Blackwell. - 1388-9842 .- 1879-0844. ; 19:3, s. 366-376
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: Symptom severity assessed by NYHA functional class and QRS duration are essential criteria for selection of heart failure (HF) patients for CRT. This study assessed the relationship between NYHA class, QRS duration, and survival in a nationwide HF registry.METHODS AND RESULTS: We studied 13 423 patients with HF in NYHA class II-IV and LVEF <40% in the Swedish Heart Failure Registry. Survival was followed via the Swedish Population Registry. Of 12 534 patients without CRT (age 71 ± 12 years, 29% women), 51% and 49% were in NYHA class II and III-IV, respectively. Patients in NYHA class II compared with class III-IV were younger (69 vs. 73 years), and had a better systolic function (49% vs. 58% with LVEF <30%), P <0.001 for all, and a favourable co-morbidity profile. QRS duration was 116 ± 29 ms in NYHA class II and 119 ± 29 ms in NYHA class III-IV with QRS ≥120 ms found in 37% vs. 44%, and an LBBB in 23% vs. 28% (P < 0.001 for all). Upon multivariable Cox regression adjusting for 40 clinically relevant variables, mortality risk was higher in NYHA class III-IV vs. class II, with a hazard ratio (HR) of 1.31, 95% confidence interval (CI) 1.23-1.40. Mortality was also higher with QRS prolongation ≥120 ms vs. narrow QRS. The HR in NYHA class II patients with non-LBBB was 1.19 (95% CI 1.05 - 1.36) and in those with LBBB it was 1.16 (95% CI 1.03-1.41). The corresponding HRs in NYHA class III-IV were 1.33 (95% CI 1.21-1.47) and 1.12 (95% CI 1.02-1.22). There was no significant interaction between the effects of NYHA class and QRS duration or morphology on mortality. Applying different scenarios to estimate guideline adherence, fewer patients with NYHA class II (range 14.4-42.6%) compared with NYHA class III-IV (18.0-45.4%) had received a CRT device when indicated.CONCLUSIONS: In HF with reduced LVEF, QRS prolongation is common and independently linked to worse survival. The increase in mortality risk associated with QRS prolongation of both LBBB and non-LBBB morphology is similar in NYHA class II and III-IV.
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  • Braunschweig, Frieder, et al. (författare)
  • Paroxysmal regular supraventricular tachycardia: the diagnostic accuracy of the transesophageal ventriculo-atrial interval.
  • 2011
  • Ingår i: Annals of Noninvasive Electrocardiology. - 1542-474X. ; 16:4, s. 327-335
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To establish the diagnostic accuracy of the transesophageal ventriculo-atrial (VA) interval in patients with paroxysmal supraventricular tachycardia (PSVT) and normal baseline electrocardiogram (ECG). Methods: The transesophageal VA interval during tachycardia was recorded in 318 patients (age 45 ± 17 years, 58% female) with PSVT and a normal surface ECG between attacks. Subsequently, all patients underwent an ablation procedure establishing the correct tachycardia diagnosis. Results: AV nodal reentrant tachycardia (AVNRT), AV reentrant tachycardia through a concealed accessory pathway (AVRT), and ectopic atrial tachycardia (EAT) were found in 213, 95, and 10 cases, respectively. Receiver operating characteristic curve analysis identified an optimal cutoff for a binary categorization of AVNRT versus AVRT/EAT at ≤80 ms (area under the curve 0.891). Owing to a biphasic distribution, AVNRT was very likely at VA intervals ≤90 ms with a sensitivity, specificity, and positive predictive value (PPV) of 87%, 91%, and 95%. In the range 91–160 ms the corresponding values for AVRT were 88%, 95%, and 88% (90%, 99%, and 98% in male patients). In the small group with VA intervals >160 ms (n = 29), the diagnosis was less clear (PPV of 67% for AVNRT). Conclusions: In patients with sudden onset regular tachycardia and a normal ECG during sinus rhythm, a transesophageal VA interval of ≤80 ms has the highest diagnostic accuracy to diagnose AVNRT versus AVRT/EAT. Overall, the biphasic distribution of VA intervals suggests considering AVNRT at 90 ms and below and AVRT between 91 and 160 ms (in particular in male patients) while the diagnosis is vague at VA intervals above 160 ms.
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  • Braunschweig, Frieder, et al. (författare)
  • Transient repolarization instability following the initiation of cardiac resynchronization therapy.
  • 2011
  • Ingår i: EP Europace. - : Oxford University Press (OUP). - 1532-2092. ; 13:9, s. 1327-1334
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims Cardiac resynchronization therapy (CRT) may cause changes in ventricular repolarization (VR), particularly in the initial phase of treatment. This study investigated the effect of CRT cessation and re-initiation on parameters of VR duration and heterogeneity at different paced heart rates. Methods Cardiac resynchronization therapy was inactivated for 2 weeks in 16 treatment responders to CRT. QT and JT intervals were measured on the surface electrocardiogram at 60, 70, and 80 bpm (randomized order) and vectorcardiography (VCG) was performed with CRT ‘on’ (day 0), ‘off’ (day 0, 1, 7, and 14) and after CRT re-initiation (day 14, 15, 16, and 21). On day 0 (‘on’) and 14 (‘off’) echocardiography, the 6 min walking distance and brain natriuretic peptide were assessed. Results The QT interval at baseline (CRT ‘on’), measured at 60, 70, and 80 bpm, was 482 ± 31, 468 ± 37, and 457 ± 39 ms, respectively, and decreased by 5, 5, and 6% during the first week following CRT cessation (all P< 0.05). Immediately after re-initiation on day 14, it increased again by 20 ± 18 (4%; P< 0.05), 34 ± 39 (8%; P< 0.01), and 16 ± 38 ms (4%, ns) followed by a gradual decrease towards previous ‘off’ levels. Similar changes were observed for the JT interval. Ventricular repolarization duration was significantly shortened by increasing the paced heart rate from 60 to 70 and 80 bpm. Vectorcardiography parameters reflecting VR gradients (ST-vector magnitude, Tarea, and Tavplan) increased significantly (by 31, 45, and 71%) after CRT cessation. A similar but non-significant pattern was observed after CRT re-initiation. Conclusion The increase in repolarization duration and gradients observed after CRT initiation suggests a transient state of VR instability that can be attenuated by programming of higher paced heart rates during the initial phase of treatment.
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  • Cabrera, Carin C., et al. (författare)
  • Increased iron absorption in patients with chronic heart failure and iron deficiency
  • 2020
  • Ingår i: Journal of Cardiac Failure. - : Elsevier BV. - 1071-9164 .- 1532-8414. ; 26:5, s. 440-443
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Iron deficiency (ID) is common in patients with chronic heart failure (CHF), but the underlying causes are not fully understood. We investigated whether ID is associated with decreased iron absorption in patients with CHF.Methods and Results: We performed an oral iron-absorption test in 30 patients and 12 controls. The patients had CHF with reduced (n = 15) or preserved (n = 15) ejection fraction and ID, defined as s- ferritin < 100 mu g/L, or s-ferritin 100-299 mu g/L and transferrin saturation < 20%. The controls had no HF or ID and were of similar age and gender. Blood samples were taken before and 2 hours after ingestion of 100 mg ferroglycin sulphate. The primary endpoint was the delta plasma iron at 2 hours. The delta plasma iron was higher in the group with HF than in the control group (median increase 83.8 [61.5;128.5] mu g/dL in HF vs 47.5 [ 30.7;61.5] mu g/dL in controls, P = 0.001), indicating increased iron absorption. There was no significant difference between the groups with preserved or reduced ejection fraction (P = 0.46).Conclusion: We found increased iron absorption in patients with CHF and ID compared to controls without ID and HF, indicating that reduced iron absorption is not a primary cause of the high prevalence of ID in patients with CHF.
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  • Das, Sarbashis, et al. (författare)
  • Transcriptomics of cardiac biopsies reveals differences in patients with or without diagnostic parameters for heart failure with preserved ejection fraction
  • 2019
  • Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Heart failure affects 2-3% of adult Western population. Prevalence of heart failure with preserved left ventricular (LV) ejection fraction (HFpEF) increases. Studies suggest HFpEF patients to have altered myocardial structure and functional changes such as incomplete relaxation and increased cardiac stiffness. We hypothesised that patients undergoing elective coronary bypass surgery (CABG) with HFpEF characteristics would show distinctive gene expression compared to patients with normal LV physiology. Myocardial biopsies for mRNA expression analysis were obtained from sixteen patients with LV ejection fraction >= 45%. Five out of 16 patients (31%) had echocardiographic characteristics and increased NTproBNP levels indicative of HFpEF and this group was used as HFpEF proxy, while 11 patients had Normal LV physiology. Utilising principal component analysis, the gene expression data clustered into two groups, corresponding to HFpEF proxy and Normal physiology, and 743 differentially expressed genes were identified. The associated top biological functions were cardiac muscle contraction, oxidative phosphorylation, cellular remodelling and matrix organisation. Our results also indicate that upstream regulatory events, including inhibition of transcription factors STAT4, SRF and TP53, and activation of transcription repressors HEY2 and KDM5A, could provide explanatory mechanisms to observed gene expression differences and ultimately cardiac dysfunction in the HFpEF proxy group.
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  • Dickstein, Kenneth, et al. (författare)
  • CRT Survey II : a European Society of Cardiology survey of cardiac resynchronisation therapy in 11 088 patients-who is doing what to whom and how?
  • 2018
  • Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 20:6, s. 1039-1051
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Cardiac resynchronisation therapy (CRT) reduces morbidity and mortality in appropriately selected patients with heart failure and is strongly recommended for such patients by guidelines. A European Society of Cardiology (ESC) CRT survey conducted in 2008-2009 showed considerable variation in guideline adherence and large individual, national and regional differences in patient selection, implantation practice and follow-up. Accordingly, two ESC associations, the European Heart Rhythm Association and the Heart Failure Association, designed a second prospective survey to describe contemporary clinical practice regarding CRT. Methods and results A survey of the clinical practice of CRT-P and CRT-D implantation was conducted from October 2015 to December 2016 in 42 ESC member countries. Implanting centres provided information about their hospital and CRT service and were asked to complete a web-based case report form collecting information on patient characteristics, investigations, implantation procedures and complications during the index hospitalisation. The 11 088 patients enrolled represented 11% of the total number of expected implantations in participating countries during the survey period; 32% of patients were aged >= 75 years, 28% of procedures were upgrades from a permanent pacemaker or implantable cardioverter-defibrillator and 30% were CRT-P rather than CRT-D. Most patients (88%) had a QRS duration >= 130 ms, 73% had left bundle branch block and 26% were in atrial fibrillation at the time of implantation. Large geographical variations in clinical practice were observed. Conclusion CRT Survey II provides a valuable source of information on contemporary clinical practice with respect to CRT implantation in a large sample of ESC member states. The survey permits assessment of guideline adherence and demonstrates variations in patient selection, management, implantation procedure and follow-up strategy.
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  • Dickstein, Kenneth, et al. (författare)
  • European Cardiac Resynchronization Therapy Survey II : rationale and design
  • 2015
  • Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 17:1, s. 137-141
  • Tidskriftsartikel (refereegranskat)abstract
    • The Cardiac Resynchronization Therapy (CRT) Survey II is a 6 months snapshot survey initiated by two ESC Associations, the European Heart Rhythm Association and the Heart Failure Association, which is designed to describe clinical practice regarding implantation of CRT devices in a broad sample of hospitals in 47 ESC member countries. The large volume of clinical and demographic data collected should reflect current patient selection, implantation, and follow-up practice and provide information relevant for assessing healthcare resource utilization in connection with CRT. The findings of this survey should permit representative benchmarking both nationally and internationally across Europe.
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  • Evans, Marc, et al. (författare)
  • The value of maintaining normokalaemia and enabling RAASi therapy in chronic kidney disease
  • 2019
  • Ingår i: BMC Nephrology. - : Springer Science and Business Media LLC. - 1471-2369. ; 20
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundPeople with chronic kidney disease (CKD) are at an increased risk of developing hyperkalaemia due to their declining kidney function. In addition, these patients are often required to reduce or discontinue guideline-recommended renin-angiotensin-aldosterone system inhibitor (RAASi) therapy due to increased risk of hyperkalaemia. This original research developed a model to quantify the health and economic benefits of maintaining normokalaemia and enabling optimal RAASi therapy in patients with CKD.MethodsA patient-level simulation model was designed to fully characterise the natural history of CKD over a lifetime horizon, and predict the associations between serum potassium levels, RAASi use and long-term outcomes based on published literature. The clinical and economic benefits of maintaining sustained potassium levels and therefore avoiding RAASi discontinuation in CKD patients were demonstrated using illustrative, sensitivity and scenario analyses.ResultsInternal and external validation exercises confirmed the predictive capability of the model. Sustained potassium management and ongoing RAASi therapy were associated with longer life expectancy (+ 2.36 years), delayed onset of end stage renal disease (+ 5.4 years), quality-adjusted life-year gains (+ 1.02 QALYs), cost savings (£3135) and associated net monetary benefit (£23,446 at £20,000 per QALY gained) compared to an absence of RAASi to prevent hyperkalaemia.ConclusionThis model represents a novel approach to predicting the long-term benefits of maintaining normokalaemia and enabling optimal RAASi therapy in patients with CKD, irrespective of the strategy used to achieve this target, which may support decision making in healthcare.
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  • Frisk, Christoffer, et al. (författare)
  • Cardiac biopsies reveal differences in transcriptomics between left and right ventricle in patients with or without diagnostic signs of heart failure
  • 2024
  • Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • New or mild heart failure (HF) is mainly caused by left ventricular dysfunction. We hypothesised that gene expression differ between the left (LV) and right ventricle (RV) and secondly by type of LV dysfunction. We compared gene expression through myocardial biopsies from LV and RV of patients undergoing elective coronary bypass surgery (CABG). Patients were categorised based on LV ejection fraction (EF), diastolic function and NT-proBNP into pEF (preserved; LVEF ≥ 45%), rEF (reduced; LVEF < 45%) or normal LV function. Principal component analysis of gene expression displayed two clusters corresponding to LV and RV. Up-regulated genes in LV included natriuretic peptides NPPA and NPPB, transcription factors/coactivators STAT4 and VGLL2, ion channel related HCN2 and LRRC38 associated with cardiac muscle contraction, cytoskeleton, and cellular component movement. Patients with pEF phenotype versus normal differed in gene expression predominantly in LV, supporting that diastolic dysfunction and structural changes reflect early LV disease in pEF. DKK2 was overexpressed in LV of HFpEF phenotype, potentially leading to lower expression levels of β-catenin, α-SMA (smooth muscle actin), and enhanced apoptosis, and could be a possible factor in the development of HFpEF. CXCL14 was down-regulated in both pEF and rEF, and may play a role to promote development of HF.
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  • Furuland, Hans, et al. (författare)
  • Serum potassium as a predictor of adverse clinical outcomes in patients with chronic kidney disease : new risk equations using the UK clinical practice research datalink
  • 2018
  • Ingår i: BMC Nephrology. - : Springer Science and Business Media LLC. - 1471-2369. ; 19
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: To address a current paucity of European data, this study developed equations to predict risks of mortality, major adverse cardiac events (MACE) and renin angiotensin-aldosterone system inhibitor (RAASi) discontinuation using time-varying serum potassium and other covariates, in a UK cohort of chronic kidney disease (CKD) patients.Methods: This was a retrospective observational study of adult CKD patients listed on the Clinical Practice Research Datalink, with a first record of CKD (stage 3a-5, pre-dialysis) between 2006 and 2015. Patients with heart failure at index were excluded. Risk equations developed using Poisson Generalized Estimating Equations were utilised to estimate adjusted incident rate ratios (IRRs) between serum potassium and adverse outcomes, and identify other predictive clinical factors.Results: Among 191,964 eligible CKD patients, 86,691 (45.16%), 30,629 (15.96%) and 9440 (4.92%) experienced at least one hyperkalaemia episode, when defined using serum potassium concentrations 5.0-< 55 mmol/L, 55-< 6.0 mmol/L and >= 6.0 mmol/L, respectively. Relative to the reference category (4.5 to < 5.0 mmol/L), adjusted IRRs for mortality and MACE exhibited U-shaped associations with serum potassium, with age being the most important predictor of both outcomes (P < 0.0001). A J-shaped association between serum potassium and RAASi discontinuation was observed; estimated glomerular filtration rate was most predictive of RAASi discontinuation (P < 0.0001).Conclusions: Hyperkalaemia was associated with increased mortality and RAASi discontinuation risk These risk equations represent a valuable tool to predict clinical outcomes among CKD patients; and identify those likely to benefit from strategies that treat hyperkalaemia, prevent RAASi discontinuation, and effectively manage serum potassium levels.
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  • Gatti, Paolo, et al. (författare)
  • What determines who gets cardiac resynchronization therapy in Europe? A comparison between ESC-HF-LT registry, SwedeHF registry, and ESC-CRT Survey II
  • 2023
  • Ingår i: European Heart Journal - Quality of Care and Clinical Outcomes. - : OXFORD UNIV PRESS. - 2058-5225 .- 2058-1742. ; 9:8, s. 741-748
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims Cardiac resynchronization therapy (CRT) is effective in heart failure with reduced ejection fraction (HFrEF) and dyssynchrony but is underutilized. In a cohort study, we identified clinical, organizational, and level of care factors linked to CRT implantation. Methods and results We included HFrEF patients fulfilling study criteria in the ESC-HF-Long Term Registry (ESC-HF-LT, n = 1031), the Swedish Heart Failure Registry (SwedeHF) (n = 5008), and the ESC-CRT Survey II (n = 11 088). In ESC-HF-LT, 36% had a CRT indication of which 47% had CRT, 53% had indication but no CRT, and the remaining 54% had no indication and no CRT. In SwedeHF, these percentages were 30, 25, 75, and 70%. Median age of patients with CRT indication and CRT present vs. absent was 68 vs. 65 years with 24% vs. 22% women in ESC-HF-LT, 76 vs. 74 years with 26% vs. 26% women in SwedeHF, and 70 years with 24% women in CRT Survey II (all had CRT). For ESC-HF-LT, independent predictors of having CRT were guideline-directed medical therapy (GDMT), atrial fibrillation (AF), prior HF hospitalization, and NYHA class. For SwedeHF, they were GDMT, age, AF, previous myocardial infarction, lower NYHA class, enrolment at university hospital, and follow-up at HF centre/Hospital. In SwedeHF, above median income and higher education level were also independently associated with having CRT. In the ESC-CRT Survey II (n = 11 088), all patients received CRT but with differences in the clinical characteristics between countries. Conclusion CRT was used in a minority of eligible patients and more used in ESC-HF-LT than in SwedeHF.
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  • Hage, Camilla, et al. (författare)
  • Metabolomic Profile in HFpEF vs HFrEF Patients
  • 2020
  • Ingår i: Journal of Cardiac Failure. - : Elsevier BV. - 1071-9164 .- 1532-8414. ; 26:12, s. 1050-1059
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Heart failure with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) are associated with metabolic derangements, which may have different pathophysiological implications.Methods and Results: In new-onset HFpEF (EF of >= 50%, n = 46) and HFrEF (EF of <40%, n = 75) patients, 109 endogenous plasma metabolites including amino acids, phospholipids and acylcarnitines were assessed using targeted metabolomics. Differentially altered metabolites and associations with clinical characteristics were explored. Patients with HFpEF were older, more often female with hypertension, atrial fibrillation, and diabetes compared with patients with HFrEF. Patients with HFpEF displayed higher levels of hydroxyproline and symmetric dimethyl arginine, alanine, cystine, and kynurenine reflecting fibrosis, inflammation and oxidative stress. Serine, cGMP, cAMP, L-carnitine, lysophophatidylcholine (18:2), lactate, and arginine were lower compared with patients with HFrEF. In patients with HFpEF with diabetes, kynurenine was higher (P = .014) and arginine lower (P = .014) vs patients with no diabetes, but did not differ with diabetes status in HFrEF. Decreasing kynurenine was associated with higher eGFR only in HFpEF (P-interaction = .020).Conclusions: Patients with new-onset HFpEF compared with patients with new-onset HFrEF display a different metabolic profile associated with comorbidities, such as diabetes and kidney dysfunction. HFpEF is associated with indices of increased inflammation and oxidative stress, impaired lipid metabolism, increased collagen synthesis, and downregulated nitric oxide signaling. Together, these findings suggest a more predominant systemic microvascular endothelial dysfunction and inflammation linked to increased fibrosis in HFpEF compared with HFrEF.
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  • Hofmarcher, Thomas, et al. (författare)
  • Cost effectiveness of implementing ESC guidelines for treatment of iron deficiency in heart failure in the Nordic countries
  • 2018
  • Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1651-2006 .- 1401-7431. ; 52:6, s. 348-355
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives. Guidelines of the European Society of Cardiology (ESC) recommend that ferritin and transferrin saturation should be tested in chronic heart failure (HF) and state that iron treatment with ferric carboxymaltose should be considered in HF patients with iron deficiency to alleviate symptoms and improve exercise tolerance and quality of life. This study evaluates the cost effectiveness of the implementation of this recommendation in four Nordic countries (Denmark, Finland, Norway, and Sweden). Design. We performed a cost-utility analysis comparing ferric carboxymaltose treatment with placebo over a one-year time period in each country. Data on healthcare resource use and health outcomes were taken from the CONFIRM-HF study and combined with country-specific unit costs. Differences in per-patient costs and quality-adjusted life years (QALYs) were calculated. Results. QALYs were higher (increase of 0.050 QALYs per patient) in the iron-treated group compared with placebo. Per-patient costs were lower in all countries (with reductions ranging from €36 to €484). Fewer hospitalizations were one key driver of these results. Another important driver was how well the new routines for iron treatment can be integrated into the current healthcare management of HF. A sensitivity analysis confirmed the results to be robust. Conclusions. Iron deficiency therapy in HF with ferric carboxymaltose compared with placebo is estimated to both improve health-related quality of life and save healthcare costs in all Nordic countries. A well-organized healthcare management of HF patients can enable the implementation of ESC-recommended treatment of iron deficiency without need for additional resources.
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25.
  • Lindberg, Felix, et al. (författare)
  • Patient profile and outcomes associated with follow-up in specialty vs. primary care in heart failure
  • 2022
  • Ingår i: ESC Heart Failure. - : Wiley Periodicals Inc. - 2055-5822. ; 9:2, s. 822-833
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims Factors influencing follow-up referral decisions and their prognostic implications are poorly investigated in patients with heart failure (HF) with reduced (HFrEF), mildly reduced (HFmrEF), and preserved (HFpEF) ejection fraction (EF). We assessed (i) the proportion of, (ii) independent predictors of, and (iii) outcomes associated with follow-up in specialty vs. primary care across the EF spectrum. Methods and results We analysed 75 518 patients from the large and nationwide Swedish HF registry between 2000-2018. Multivariable logistic regression models were fitted to identify the independent predictors of planned follow-up in specialty vs. primary care, and multivariable Cox models to assess the association between follow-up type and outcomes. In this nationwide registry, 48 115 (64%) patients were planned for follow-up in specialty and 27 403 (36%) in primary care. The median age was 76 [interquartile range (IQR) 67-83] years and 27 546 (36.5%) patients were female. Key independent predictors of planned follow-up in specialty care included optimized HF care, that is follow-up in a nurse-led HF clinic [odds ratio (OR) 4.60, 95% confidence interval (95% CI) 4.41-4.79], use of HF devices (OR 3.99, 95% CI 3.62-4.40), beta-blockers (OR 1.39, 95% CI 1.32-1.47), renin-angiotensin system/angiotensin-receptor-neprilysin inhibitors (OR 1.21, 95% CI 1.15-1.27), and mineralocorticoid receptor antagonists (OR 1.31, 95% CI 1.26-1.37); and more severe HF, that is higher NT-proBNP (OR 1.13, 95% CI 1.06-1.20) and NYHA class (OR 1.13, 95% CI 1.08-1.19). Factors associated with lower likelihood of follow-up in specialty care included older age (OR 0.29, 95% CI 0.28-0.30), female sex (OR 0.89, 95% CI 0.86-0.93), lower income (OR 0.79, 95% CI 0.76-0.82) and educational level (OR 0.77, 95% CI 0.73-0.81), higher EF [HFmrEF (OR 0.65, 95% CI 0.62-0.68) and HFpEF (OR 0.56, 95% CI 0.53-0.58) vs. HFrEF], and higher comorbidity burden, such as presence of kidney disease (OR 0.91, 95% CI 0.87-0.95), atrial fibrillation (OR 0.85, 95% CI 0.81-0.89), and diabetes mellitus (OR 0.92, 95% CI 0.88-0.96). A planned follow-up in specialty care was independently associated with lower risk of all-cause [hazard ratio (HR) 0.78, 95% CI 0.76-0.80] and cardiovascular death (HR 0.76, 95% CI 0.73-0.78) across the EF spectrum, but not of HF hospitalization (HR 1.06, 95% CI 1.03-1.10). Conclusions In a large nationwide HF population, referral to specialty care was linked with male sex, younger age, lower EF, lower comorbidity burden, better socioeconomic environment and optimized HF care, and associated with better survival across the EF spectrum. Our findings highlight the need for greater and more equal access to HF specialty care and improved quality of primary care.
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26.
  • Lindberg, Felix, et al. (författare)
  • Trajectories in New York Heart Association functional class in heart failure across the ejection fraction spectrum : data from the Swedish Heart Failure Registry
  • 2022
  • Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 24:11, s. 2093-2104
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims To investigate incidence, predictors and prognostic implications of longitudinal New York Heart Association (NYHA) class changes (i.e. improving or worsening vs. stable NYHA class) in heart failure (HF) across the ejection fraction (EF) spectrum. Methods and results From the Swedish HF Registry, 13 535 patients with EF and >= 2 NYHA class assessments were considered. Multivariable multinomial regressions were fitted to identify the independent predictors of NYHA change. Over a 1-year follow-up, 69% of patients had stable, 17% improved, and 14% worsened NYHA class. Follow-up in specialty care predicted improving NYHA class, whereas an in-hospital patient registration, lower EF, renal disease, lower mean arterial pressure, older age, and longer HF duration predicted worsening. The association between NYHA change and subsequent outcomes was assessed with multivariable Cox models. When adjusting for the NYHA class at baseline, improving NYHA class was independently associated with lower while worsening with higher risk of all-cause and cardiovascular mortality, and first HF hospitalization. After adjustment for the NYHA class at follow-up, NYHA class change did not predict morbidity/mortality. NYHA class assessment at baseline and follow-up predicted morbidity/mortality on top of the changes. Results were consistent across the EF spectrum. Conclusion In a large real-world HF population, NYHA class trajectories predicted morbidity/mortality after extensive adjustments. However, the prognostic role was entirely explained by the resulting NYHA class, i.e. the follow-up value. Our results highlight that considering one-time NYHA class assessment, rather than trajectories, might be the preferable approach in clinical practice and for clinical trial design.
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27.
  • Linde, Cecilia, et al. (författare)
  • Baseline characteristics of 547 new onset heart failure patients in the PREFERS heart failure study
  • 2022
  • Ingår i: ESC Heart Failure. - : John Wiley & Sons. - 2055-5822. ; 9:4, s. 2125-2138
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim We present the baseline characteristics of the PREFERS Stockholm epidemiological study on the natural history and course of new onset heart failure (HF) aiming to improve phenotyping focusing on HF with preserved left ventricular ejection fraction (HFpEF) pathophysiology.Methods and results New onset HF patients diagnosed in hospital or at outpatient HF clinics were included at five Stockholm hospitals 2015-2018 and characterized by N-terminal pro brain natriuretic peptide (NT-proBNP), biomarkers, echocardiography, and cardiac magnetic resonance imaging (subset). HFpEF [left ventricular ejection fraction (LVEF) >= 50%) was compared with HF with mildly reduced LVEF (HFmrEF; LVEF 41-49%) and with HF with reduced LVEF (HFrEF; LVEF <= 40%). We included 547 patients whereof HFpEF (n = 137; 25%), HFmrEF (n = 61; 11%), and HFrEF (n = 349; 64%). HFpEF patients were older (76; 70-81 years; median; interquartile range) than HFrEF (67; 58-74; P < 0.001), more often women (49% vs. 30%; P < 0.001), and had significantly higher comorbidity burden. They more often had atrial fibrillation, hypertension, and renal dysfunction. NT-proBNP was lower in HFpEF (896; 462-1645 ng/L) than in HFrEF (1160; 563-2370; P = 0.005). In HFpEF, left ventricular (LV) diameters and volumes were smaller (P < 0.001) and septa! and posterior wall thickness and relative wall thickness higher (P < 0.001). E/e >= 14 was present in 26% of HFpEF vs. 32% of HFrEF (P = 0.017) and left atrial volume index > 34 mL/m(2) in 57% vs. 61% (P = 0.040). HFmrEF patients were intermediary between HFpEF and HFrEF for LV mass, LV volumes, and RV volumes but had the highest proportion of left ventricular hypertrophy and the lowest proportion of elevated E/e.Conclusions Phenotype data in new onset HF patients recruited in a broad clinical setting showed that 25% had HFpEF, were older, more often women, and had greater comorbidity burden. PREFERS is well suited to further explore biomarker and imaging components of HFpEF pathophysiology and may contribute to the emerging knowledge of HF epidemiology.
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28.
  • Linde, Cecilia, et al. (författare)
  • Gender, underutilization of cardiac resynchronization therapy, and prognostic impact of QRS prolongation and left bundle branch block in heart failure.
  • 2015
  • Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 17:3, s. 424-431
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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29.
  • Linde, Cecilia, et al. (författare)
  • Real-World Associations of Renin-Angiotensin-Aldosterone System Inhibitor Dose, Hyperkalemia, and Adverse Clinical Outcomes in a Cohort of Patients With New-Onset Chronic Kidney Disease or Heart Failure in the United Kingdom
  • 2019
  • Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 8:22
  • Tidskriftsartikel (refereegranskat)abstract
    • Background-Dosing of renin-angiotensin-aldosterone system inhibitors (RAASi) may be modified to manage associated hyperkalemia risk; however, this approach could adversely affect cardiorenal outcomes. This study investigated real-world associations of RAASi dose, hyperkalemia, and adverse clinical outcomes in a large cohort of UK cardiorenal patients. Methods and Results-This observational study included RAASi-prescribed patients with new-onset chronic kidney disease (n=100 572) or heart failure (n=13 113) first recorded between January 2006 and December 2015 in Clinical Practice Research Datalink and linked Hospital Episode Statistics databases. Odds ratios associating hyperkalemia and RAASi dose modification were estimated using logistic generalized estimating equations with normal (<5.0 mmol/L) serum potassium level as the reference category. Patients with serum potassium >= 5.0 mmol/L had higher risk of RAASi down-titration (adjusted odds ratios, chronic kidney disease: 1.79 [95% CI, 1.64-1.96]; heart failure: 1.33 [95% CI, 1.08-1.62]). Poisson models were used to estimate adjusted incident rate ratios of adverse outcomes based on total RAASi exposure (<50% and >= 50% of the guideline-recommended RAASi dose). Incidence of major adverse cardiac events and mortality was consistently higher in the lower dose group (adjusted incident rate ratios: chronic kidney disease: 5.60 [95% CI, 5.29-5.93] for mortality and 1.60 [95% CI, 1.55-1.66] for nonfatal major adverse cardiac events; heart failure: 7.34 [95% CI, 6.35-8.48] for mortality and 1.85 [95% CI, 1.71-1.99] for major adverse cardiac events). Conclusions-The results of this real-world analysis highlight the potential negative impact of suboptimal RAASi dosing and the need for strategies that allow patients to be maintained on appropriate therapy, avoiding RAASi dose modification or discontinuation.
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30.
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31.
  • Linde, Cecilia, et al. (författare)
  • Serum potassium and clinical outcomes in heart failure patients : results of risk calculations in 21 334 patients in the UK
  • 2019
  • Ingår i: ESC Heart Failure. - : Wiley. - 2055-5822. ; 6:2, s. 280-290
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: At present, the clinical burden of hypokalaemia and hyperkalaemia among European heart failure patients, and relationships between serum potassium and adverse clinical outcomes in this population, is not well characterized. The aim of this study was to investigate associations between mortality, major adverse cardiac events, and renin–angiotensin–aldosterone system inhibitor (RAASi) discontinuation across serum potassium levels, in a UK cohort of incident heart failure patients.Methods and results: This was a retrospective observational cohort study of newly diagnosed heart failure patients listed in the Clinical Practice Research Datalink, with a first record of heart failure (index date) between 2006 and 2015. Hypokalaemia and hyperkalaemia episodes were defined as the number of serum potassium measurements exceeding each threshold (<3.5, ≥5.0, ≥5.5, and ≥6.0 mmol/L), without such a measurement in the preceding 7 days. Risk equations developed using Poisson generalized estimating equations were utilized to estimate adjusted incident rate ratios (IRRs) relating serum potassium and clinical outcomes (death, major adverse cardiac event, and RAASi discontinuation). Among 21,334 eligible heart failure patients, 1969 (9.2%), 7648 (35.9%), 2725 (12.8%), and 763 (3.6%) experienced episodes of serum potassium <3.5, ≥5.0, ≥5.5, and ≥6.0 mmol/L, respectively. The adjusted IRRs for mortality exhibited a U‐shaped association pattern with serum potassium. Relative to the reference category (4.5 to <5.0 mmol/L), adjusted IRRs for mortality were estimated as 1.98 (95% confidence interval: 1.69–2.33), 1.23 (1.12–1.36), 1.35 (1.14–1.60), and 3.02 (2.28–4.02), for patients with serum potassium <3.5, ≥5.0 to <5.5, ≥5.5 to <6.0, and ≥6.0 mmol/L, respectively. The adjusted IRRs for major adverse cardiac events demonstrated a non‐statistically significant relationship with serum potassium. Discontinuation of RAASi therapy exhibited a J‐shaped trend in association with serum potassium. Compared with the reference category (4.5 to <5.0 mmol/L), adjusted IRRs were estimated as 1.07 (0.89–1.28) in patients with serum potassium <3.5 mmol/L, increasing to 1.32 (1.14–1.53) and 2.19 (1.63–2.95) among those with serum potassium ≥5.5 to <6.0 and ≥6.0 mmol/L, respectively.Conclusions: In UK patients with new onset heart failure, both hypokalaemia and hyperkalaemia were associated with increased mortality risk, and hyperkalaemia was associated with increased likelihood of RAASi discontinuation. Our results demonstrate the potential importance of serum potassium monitoring for heart failure outcomes and management.
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32.
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33.
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34.
  • Ljung Faxén, Ulrika, et al. (författare)
  • HFpEF and HFrEF Display Different Phenotypes as Assessed by IGF-1 and IGFBP-1
  • 2017
  • Ingår i: Journal of Cardiac Failure. - : Elsevier BV. - 1071-9164 .- 1532-8414. ; 23:4, s. 293-303
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundAnabolic drive is impaired in heart failure with reduced ejection fraction (HFrEF) but insufficiently studied in heart failure with preserved ejection fraction (HFpEF). Insulin-like growth factor 1 (IGF-1) mediates growth hormone effects and IGF binding protein 1 (IGFBP-1) regulates IGF-1 activity. We tested the hypothesis that HFpEF and HFrEF are similar with regard to IGF-1 and IGFBP-1.Methods and ResultsIn patients with HFpEF (n = 79), HFrEF (n = 85), and controls (n = 136), we analyzed serum IGF-1 and IGFBP-1 concentrations, correlations, and associations with outcome. Age-standardized scores of IGF-1 were higher in HFpEF, median arbitrary units (interquartile range); 1.21 (0.57–1.96) vs HFrEF, 0.09 (-1.40–1.62), and controls, 0.22 (-0.47-0.96), P overall <.001. IGFBP-1 was increased in HFpEF, 48 (28–79), and HFrEF, 65 (29–101), vs controls, 27(14–35) µg/L, P overall <.001. These patterns persisted after adjusting for metabolic and HF severity confounders. IGF-1 was associated with outcomes in HFrEF, hazard ratio per natural logarithmic increase in IGF-1 SD score 0.51 (95% confidence interval 0.32–0.82, P = .005), but not significantly in HFpEF. IGFBP-1 was not associated with outcomes in either HFpEF nor HFrEF.ConclusionHFpEF and HFrEF phenotypes were similar with regard to increased IGFBP-1 concentrations but differed regarding IGF-1 levels and prognostic role. HFrEF and HFpEF may display different impairment in anabolic drive.
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35.
  • Ljung Faxen, Ulrika, et al. (författare)
  • HFpEF and HFrEF exhibit different phenotypes as assessed by leptin and adiponectin
  • 2017
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 228, s. 709-716
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Heart failure with reduced ejection fraction (HFrEF) exhibits a reverse metabolic profile. Whether this profile exists in HF with preserved ejection fraction (HFpEF) is unknown. We tested the hypothesis that HFpEF and HFrEF are similar regarding concentrations of and prognostic impact of leptin and adiponectin.Methods: In patients with HFpEF(n = 79), HFrEF(n = 84), and controls(n = 71), we analyzed serum leptin and adiponectin concentrations, their correlations, and associations with outcome.Results: Leptin levels in HFpEF and HFrEF were increased (p < 0.05) compared to controls; with the highest levels in HFpEF, median (IQR), 23.1 (10.2-51.0), vs. HFrEF 15.0 (6.2-33.2), and vs. controls 10.8 (5.4-18.9) ng/mL. There was no difference between HFpEF and HFrEF p=0.125 (adjusted for gender, BMI and age). Leptin was inversely associated with NT-proBNP (r = -0.364 p = 0.001) and associated with better outcome in HFrEF (HR per ln increase of leptin 0.76, 95% CI 0.58-0.99, p = 0.044) but not in HFpEF.Crude levels of adiponectin were similar in HFpEF: 11.8 (7.9-20.1), HFrEF: 13.7 (7.0-21.1), and controls: 10.5 (7.4-15.1) mu g/L. In men, adjusted similarly as leptin, there was no difference between HFpEF and HFrEF, p = 0.310 but, compared to controls, higher levels in HFpEF (p - 0.044) and HFrEF (p - 0.001). Adiponectin correlated positively with NT-proBNP; r = 0.396 p < 0.001 and higher levels were associated with adverse outcome only in HFrEF (HR per ln increase 2.88 (95% CI 1.02-8.14, p = 0.045).Conclusion: HFpEF and HFrEF share elevated levels of leptin and adiponectin. However, the concept of reverse metabolic profile could not be confirmed in HFpEF, suggesting that HFpEF might have a conventional metabolic profile, rather than a distinct HF syndrome.
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36.
  • Ljung Faxen, Ulrika, et al. (författare)
  • N-terminal pro-B-type natriuretic peptide in chronic heart failure: The impact of sex across the ejection fraction spectrum
  • 2019
  • Ingår i: International Journal of Cardiology. - : ELSEVIER IRELAND LTD. - 0167-5273 .- 1874-1754. ; 21, s. 225-225
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The aim was to assess sex-specific differences in N-terminal B-type natriuretic peptide (NT-proBNP) regarding concentrations, predictors of high concentrations, and prognostic role, in a large and unselected population with chronic heart failure (HF) with preserved (HFpEF), mid-range (HFmrEF), and reduced ejection fraction (HFrEF). Methods and results: In 9847 outpatients with HFpEF, HFmrEF, and HFrEF (49 vs. 35 vs. 25% females, respectively) from the Swedish HF Registry, median NT-proBNP concentrations were 1598 ng/L in females vs. 1310 ng/L in males in HFpEF, 1764 vs. 1464 ng/L in HFmrEF, and 2543 vs. 2226 ng/L in HFrEF (p amp;lt; 0.05 for all). The differences persisted after multiple adjustment. The largest sex-difference in NT-proBNP levels was observed in HFpEF with sinus rhythm, where median concentrations were 1.4 folds higher in females (923 vs. 647 ng/L). Independent predictors of NT-proBNP levels (defined as above the different medians according to sex and HF phenotype) were overall consistent across sexes and EF. NT-proBNP levels were similarly associated with risk of all-cause death/HF hospitalization in both sexes regardless of EF. Conclusion: Concentrations of NT-proBNPwere higher in females across the EF spectrum, with larger relative differences in HFpEF with sinus rhythm. However, similar predictors of high levels were observed in both sexes. There were no sex-differences in the prognostic role of NT-proBNP. These findings support the use of NT-proBNP for prognostic purposes in chronic HF, regardless of sex. (c) 2019 Elsevier B.V. All rights reserved.
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37.
  • Lund, Lars H., et al. (författare)
  • Age, prognostic impact of QRS prolongation and left bundle branch block, and utilization of cardiac resynchronization therapy: findings from 14713 patients in the Swedish Heart Failure Registry
  • 2014
  • Ingår i: European Journal of Heart Failure. - : Oxford University Press (OUP): Policy B / Wiley. - 1388-9842 .- 1879-0844. ; 16:10, s. 1073-1081
  • Tidskriftsartikel (refereegranskat)abstract
    • AimsAge is not a contraindication to cardiac resynchronization therapy (CRT), but the prevalence and prognostic impact of QRS prolongation with intraventricular conduction delay (IVCD) and left bundle branch block (LBBB), as well as CRT utilization, may differ with age. We tested the hypotheses that in the elderly: (i) IVCD and LBBB are more prevalent, (ii) IVCD and LBBB are more harmful, and (iii) CRT is underutilized. Methods and resultsWe studied 14713 patients with ejection fraction 39% in the Swedish Heart Failure Registry and divided into age groups 65years, 66-80years and greater than80years. Among 13782 patients without CRT, IVCD was present in the three age groups in 11% vs. 15% vs. 19% and LBBB was present in 20% vs. 27% vs. 28%, respectively, (Pless than0.001). The multivariable hazard ratio (HR) for all-cause mortality over a median (interquartile range) follow-up of 29 (12-53) months for IVCD vs. narrow QRS was 1.31 (1.06-1.63, P=0.013) in the 65year group, 1.32 (1.17-1.47, Pless than0.001) in the 66-80year group, and 1.26 (1.21-1.41, pless than0.001) in the greater than80year group. For LBBB vs. narrow QRS it was 1.29 (1.07-1.56, P=0.009), 1.17 (1.06-1.30, P=0.002), and 1.10 (0.99-1.22, P=0.091), respectively. The adjusted P for interaction between age and QRS morphology was 0.664. In the three age groups, CRT was present in 6% vs. 8% vs. 4% and absent but with indication in 23% vs. 32% vs. 37%, respectively (Pless than0.001). ConclusionsBoth IVCD and LBBB were more common with increasing age and were similarly strong independent predictors of mortality and in all ages. The underutilization of CRT was worse with increasing age.
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38.
  • Lund, Lars H, et al. (författare)
  • Association between demographic, organizational, clinical, and socio-economic characteristics and underutilization of cardiac resynchronization therapy : results from the Swedish Heart Failure Registry.
  • 2017
  • Ingår i: European Journal of Heart Failure. - : John Wiley & Sons. - 1388-9842 .- 1879-0844. ; 19:10, s. 1270-1279
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: Cardiac resynchronization therapy (CRT) improves outcomes in heart failure (HF) but may be underutilized. The reasons are unknown.METHODS AND RESULTS: We linked the Swedish Heart Failure Registry to national registries with ICD-10 (International Classification of Diseases-10th Revision) co-morbidity diagnoses and demographic and socio-economic data. In patients with EF ≤39% and NYHA II-IV, we assessed prevalence of CRT indication and CRT use. In those with CRT indication, we assessed the association between 37 potential baseline covariates and CRT non-use using multivariable generalized estimating equation (GEE) models. Of 12 807 patients (mean age 71 ± 12 years, 28% female), 841 (7%) had CRT, 3094 (24%) had an indication for but non-use of CRT, and 8872 (69%) had no indication. Important variables independently associated with CRT non-use were: HF duration <6 months [risk ratio (RR) 1.21, 95% confidence interval (CI) 1.17-1.24]; non-cardiology planned follow-up (RR 1.14, 95% CI 1.09-1.18); age >75 years (RR 1.13, 95% CI 1.09-1.18); non-cardiology care at baseline (RR 1.10, 95% CI 1.07-1.14); small-town non-university centre (RR 1.08, 95% CI 1.05-1.12); female sex (RR 1.07 95% CI 1.03-1.10) (all P < 0.05); as was absence of AF, living alone; psychiatric diagnosis; smoking; and non-use of HF drugs. Education, income, cancer, or HF characteristics were not independently associated with CRT non-use.CONCLUSION: In this population-wide HF registry, CRT was underutilized. Non-use was associated mostly with demographic and organizational, but not clinical or socio-economic factors. This calls for programmes to raise awareness of CRT indications and improve access and referrals to cardiology specialists.
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39.
  • Lund, Larrs H., et al. (författare)
  • Prevalence, correlates, and prognostic significance of QRS prolongation in heart failure with reduced and preserved ejection fraction
  • 2013
  • Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 34:7, s. 529-539
  • Tidskriftsartikel (refereegranskat)abstract
    • AimsThe 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 resultsWe 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.ConclusionQRS 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.
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40.
  • Matan, Dmitri, et al. (författare)
  • Extracellular vesicles in heart failure : A study in patients with heart failure with preserved ejection fraction or heart failure with reduced ejection fraction characteristics undergoing elective coronary artery bypass grafting
  • 2022
  • Ingår i: Frontiers in Cardiovascular Medicine. - : Frontiers Media S.A.. - 2297-055X. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • AimsExtracellular vesicles (EVs) were investigated as potential biomarkers associated with heart failure (HF) pathophysiology in patients undergoing elective coronary artery bypass surgery characterized by HF phenotype. Materials and methodsPatients with preoperative proxy-diagnoses of HF types i.e., preserved (HFpEF; n = 19) or reduced ejection fraction (HFrEF; n = 20) were studied and compared to patients with normal left ventricular function (n = 42). EVs in plasma samples collected from the coronary sinus, an arterial line, and from the right atrium were analyzed by flow cytometry. We studied EVs of presumed cardiomyocyte origin [EVs exposing Connexin-43 + Caveolin-3 (Con43 + Cav3) and Connexin-43 + Troponin T (Con43 + TnT)], of endothelial origin [EVs exposing VE-Cadherin (VE-Cad)] and EVs exposing inflammatory markers [myeloperoxidase (MPO) or pentraxin3 (PTX3)]. ResultsMedian concentrations of EVs exposing Con43 + TnT and Con43 + Cav3 were approximately five to six times higher in coronary sinus compared to radial artery indicative of cardiac release. Patients with HFrEF had high trans-coronary gradients of both Con43 + TnT and Con43 + Cav3 EVs, whereas HFpEF had elevated gradients of Con43 + Cav3 EVs but lower gradients of Con43 + TnT. Coronary sinus concentrations of both Con43 + TnT and Con43 + Cav3 correlated significantly with echocardiographic and laboratory measures of HF. MPO-EV concentrations were around two times higher in the right atrium compared to the coronary sinus, and slightly higher in HFpEF than in HFrEF. EV concentrations of endothelial origin (VE-Cad) were similar in all three patient groups. ConclusionCon43 + TnT and Con43 + Cav3 EVs are released over the heart indicating cardiomyocyte origin. In HFrEF the EV release profile is indicative of myocardial injury and myocardial stress with elevated trans-coronary gradients of both Con43 + TnT and Con43 + Cav3 EVs, whereas in HFpEF the profile indicates myocardial stress with less myocardial injury.
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41.
  • Mullens, Wilfried, et al. (författare)
  • Integration of implantable device therapy in patients with heart failure. A clinical consensus statement from the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC)
  • 2024
  • Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844.
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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42.
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43.
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44.
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45.
  • Nilsson, Christer, et al. (författare)
  • Characterization of therapy-related acute myeloid leukemia : increasing incidence and prognostic implications
  • 2023
  • Ingår i: Haematologica. - : Ferrata Storti Foundation. - 0390-6078 .- 1592-8721. ; 108:4, s. 1015-1025
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies of therapy-related AML (t-AML) are usually performed in selected cohorts and reliable incidence rates are lacking. In this study, we characterized, defined the incidence over time and studied prognostic implications in all t-AML patients diagnosed in Sweden between 1997 and 2015. Data were retrieved from nationwide population-based registries. In total, 6,779 AML patients were included in the study, of whom 686 (10%) had t-AML. The median age for t-AML was 71 years and 392 (57%) patients were females. During the study period, the incidence of t-AML almost doubled with a yearly increase in t-AML of 4.5% (95% confidence interval: 2.8%-6.2%), which contributed significantly to the general increase in AML incidence over the study period. t-AML solidly constituted over 10% of all AML cases during the later period of the study. Primary diagnoses with the largest increase in incidence and decrease in mortality rate during the study period (i.e., breast and prostate cancer) contributed significantly to the increased incidence of t-AML. In multivariable analysis, t-AML was associated with poorer outcome in cytogenetically intermediate-and adverse-risk cases but t-AML had no significant impact on outcome in favorable-risk AML, including core binding leukemias, acute promyelocytic leukemia and AML with mutated NPM1 without FLT3-ITD. We conclude that there is a strong increase in incidence in t-AML over time and that t-AML constitutes a successively larger proportion of the AML cases. Furthermore, we conclude that t-AML confers a poor prognosis in cytogenetically intermediate-and adverse-risk, but not in favorable-risk AML.
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46.
  • Normand, Camilla, et al. (författare)
  • Adherence to ESC cardiac resynchronization therapy guidelines : findings from the ESC CRT Survey II
  • 2020
  • Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 22:6, s. 932-938
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with heart failure (HF) and electrical dyssynchrony. The European Society of Cardiology (ESC) Guidelines provide evidence-based recommendations indicating optimal patient selection for CRT implantation in both the 2013 European Heart Rhythm Association (EHRA) and the 2016 Heart Failure Association (HFA) Guidelines. We assessed the adherence to guidelines and identified factors associated with guideline adherence.METHODS AND RESULTS: In 2016, the HFA and EHRA conducted the CRT Survey II in 42 ESC countries. The data collected were sufficient to evaluate adherence to guidelines in 8021 patients. Of these, 67% had a Class I guideline indication for CRT implantation, which was significantly correlated with female gender (1.70, P < 0.0001), age <75 years (1.55, P < 0.0001), non-ischaemic HF aetiology (1.22, P < 0.0001), and elective admission (1.87, P < 0.0001). A further 26% of implants had a Class IIa indication, 5% IIb and only 2% a contraindication to CRT-a Class III indication. Patients implanted under Level IIa indications were much more likely to have more comorbidities than patients implanted under Level I indications. However, there were large variations in guideline adherence between ESC countries.CONCLUSION: Implanters in ESC member states demonstrate a high degree of adherence to ESC guidelines with 98% of implants having a documented Class I, IIa or IIb indication. Cardiac resynchronization therapy implantation without a Class I indication was more likely in men, patients age ≥75 years, with HF of ischaemic origin and in patients admitted to hospital acutely.
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47.
  • Normand, Camilla, et al. (författare)
  • Cardiac resynchronization therapy pacemaker or cardiac resynchronization therapy defibrillator : what determines the choice?-findings from the ESC CRT Survey II
  • 2019
  • Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 21:6, s. 918-927
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: The decision to implant a cardiac resynchronization therapy pacemaker (CRT-P) or a cardiac resynchronization therapy defibrillator (CRT-D) may be challenging. There are no clear guideline recommendations as no randomized study of cardiac resynchronization therapy (CRT) has been designed to compare the effects of CRT-P with those of CRT-D on patients' outcomes. In the CRT Survey II, we studied patient and implantation centre characteristics associated with the choice of CRT-P vs. CRT-D.METHODS AND RESULTS: Clinical practice data from 10 692 patients undergoing CRT implantation of whom 7467 (70%) patients received a CRT-D and 3225 (30%) received a CRT-P across 42 ESC countries were collected and analysed between October 2015 and January 2017. Factors favouring the selection of CRT-P implantation included age >75 years, female gender, non-ischaemic heart failure (HF) aetiology, New York Heart Association functional Class III/IV symptoms, left ventricular ejection fraction >25%, atrial fibrillation, atrioventricular (AV) block II/III, and implantation in a university hospital.CONCLUSION: In a large cohort from the CRT Survey II, we found that patients allocated to receive CRT-P exhibited particular phenotypes with more symptomatic HF, more frequent comorbidities, advanced age, female gender, non-ischaemic HF aetiology, atrial fibrillation, and evidence of AV block. There were substantial differences in the proportion of patients allocated to receive CRT-P vs. CRT-D between countries.
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48.
  • Schrage, Benedikt, et al. (författare)
  • Association Between Use of Primary-Prevention Implantable Cardioverter-Defibrillators and Mortality in Patients With Heart Failure A Prospective Propensity Score-Matched Analysis From the Swedish Heart Failure Registry
  • 2019
  • Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 140:19, s. 1530-1539
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Most randomized trials on implantable cardioverter-defibrillator (ICD) use for primary prevention of sudden cardiac death in heart failure with reduced ejection fraction enrolled patients amp;gt;20 years ago. We investigated the association between ICD use and all-cause mortality in a contemporary heart failure with reduced ejection fraction cohort and examined relevant subgroups. Methods: Patients from the Swedish Heart Failure Registry fulfilling the European Society of Cardiology criteria for primary-prevention ICD were included. The association between ICD use and 1-year and 5-year all-cause and cardiovascular (CV) mortality was assessed by Cox regression models in a 1:1 propensity score-matched cohort and in prespecified subgroups. Results: Of 16 702 eligible patients, only 1599 (10%) had an ICD. After matching, 1305 ICD recipients were compared with 1305 nonrecipients. ICD use was associated with a reduction in all-cause mortality risk within 1 year (hazard ratio, 0.73 [95% CI, 0.60-0.90]) and 5 years (hazard ratio, 0.88 [95% CI, 0.78-0.99]). Results were consistent in all subgroups including patients with versus without ischemic heart disease, men versus women, those aged amp;lt;75 versus amp;gt;= 75 years, those with earlier versus later enrollment in the Swedish heart failure registry, and patients with versus without cardiac resynchronization therapy. Conclusions: In a contemporary heart failure with reduced ejection fraction population, ICD for primary prevention was underused, although it was associated with reduced short- and long-term all-cause mortality. This association was consistent across all the investigated subgroups. These results call for better implementation of ICD therapy.
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49.
  • Schrage, Benedikt, et al. (författare)
  • Cardiac resynchronization therapy with or without defibrillator in patients with heart failure
  • 2022
  • Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 24:1, s. 48-57
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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50.
  • Schrage, Benedikt, et al. (författare)
  • Predictors of primary prevention implantable cardioverter-defibrillator use in heart failure with reduced ejection fraction : impact of the predicted risk of sudden cardiac death and all-cause mortality
  • 2022
  • Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 24:7, s. 1212-1222
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims Use of implantable cardioverter-defibrillators (ICD) for primary prevention of sudden cardiac death (SCD) in heart failure with reduced ejection fraction (HFrEF) is limited. We aimed to investigate barriers to ICD use in HFrEF while considering the predicted risk of mortality and SCD. Method and results Patients from the SwedeHF registered in 2011-2018 and with an indication for primary prevention ICD were analysed. The Seattle Proportional Risk and Seattle Heart Failure Models were used to predict the proportional SCD and all-cause mortality risk, respectively. A multivariable logistic regression model was fitted to identify independent predictors of ICD use/non-use; Cox regression models to evaluate the interaction between predicted SCD/mortality risk and ICD use for mortality. Of 13 475 patients, only 15.5% had an ICD. Those with higher predicted proportional SCD risk (>45%) had an similar to 80% higher likelihood to have an ICD. Other predictors of non-use were follow-up in primary versus specialty care, higher comorbidity burden and lower socioeconomic status. ICD use was associated with lower mortality only in patients with higher predicted SCD and lower mortality risk (34% and 37% relative risk reduction for 3-year all-cause and cardiovascular mortality, respectively). In this subgroup of patients, underuse of ICD was 81.8%. Conclusion In a contemporary registry, only 15.5% of patients with an indication for primary prevention ICD received the device. While a high predicted proportional SCD risk was appropriately linked to ICD use, the lack of specialized follow-up, higher comorbidity burden, and lower socioeconomic status were major unjustified impediments to implementation. Our findings suggest areas for improving ICD use for primary prevention of SCD in clinical practice.
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