Karl Swedberg

University of Gothenburg | GU · Department of Molecular and Clinical Medicine

Aims: Early start and patient profile-oriented heart failure (HF) management has been recommended. In this post hoc analysis from the SHIFT trial, we analysed the treatment effects of ivabradine in HF patients with systolic blood pressure (SBP) < 110 mmHg, resting heart rate (RHR) ≥ 75 b.p.m., left ventricular ejection fraction (LVEF) ≤ 25%, New Y...

Aims: Stroke is an important problem in patients with heart failure (HF), but the intersection between the two conditions is poorly studied across the range of ejection fraction. The prevalence of history of stroke and related outcomes were investigated in patients with HF. Methods and results: Individual patient meta-analysis of seven clinical...

Background: It is uncertain how much candidate biomarkers improve risk prediction when added to comprehensive models including routinely collected clinical and laboratory variables in heart failure. Methods: Aldosterone, cystatin C, high sensitivity-troponin T (hs-TnT), galectin-3, growth differentiation factor-15 (GDF-15), kidney injury molecul...

Aims: In the SHIFT (Systolic Heart failure treatment with the If inhibitor ivabradine Trial, ISRCTN70429960) study, ivabradine reduced cardiovascular death or heart failure (HF) hospitalizations in patients with heart failure and reduced ejection fraction (HFrEF) in sinus rhythm and with a heart rate (HR) ≥70 bpm. In this study, we sought to deter...

Aims Multimorbidity, the coexistence of two or more chronic conditions, is synonymous with heart failure(HF). How risk related to comorbidities compare at individual and population levels is unknown. The aim of this study is to examine the risk related to comorbidities, alone and in combination, both at individual and population levels. Methods Us...

Aims: The 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation combining creatinine and cystatin C provides a better estimation of glomerular filtration rate (GFR) compared to the creatinine-only equation. Methods and results: CKD-EPI creatinine-cystatin C equation (creatinine-cystatin) was compared to creatinine-only (creat...

Background: Anemia is common in patients with heart failure with reduced ejection fraction and is associated with poor clinical outcomes. Renin-angiotensin system blockers lower hemoglobin and may induce anemia. Objectives: The authors investigated whether concomitant neprilysin inhibition might ameliorate this effect of renin-angiotensin system...

Background Healthcare and welfare systems worldwide are unprepared to accommodate the growing population of older people. Simultaneously, the cost of reactive care for older people is increasing. However, healthcare systems in many countries are reforming towards integrated and person-centred care with a focus on health promotion and proactive acti...

Aims: Although body mass index (BMI) is the most commonly used anthropometric measure, newer indices such as the waist-to-height ratio, better reflect the location and amount of ectopic fat, as well as the weight of the skeleton, and may be more useful. Methods and results: The prognostic value of several newer anthropometric indices was compare...

Importance Heart failure (HF) treatment recommendations are centered on New York Heart Association (NYHA) classification, such that most apparently asymptomatic patients are not eligible for disease-modifying therapies. Objectives To assess within-patient variation in NYHA classification over time, the association between NYHA class and an objecti...

Background Estimated glomerular filtration rate (eGFR) is a key determinant of eligibility for many life-saving therapies in HFrEF. Recently, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) provided new equations based on creatinine (CKD-EPIcr), cystatin C (CKD-EPIcys) or both (CKD-EPIcyscr) that do not include race. These new equat...

Background Although multiple novel biomarkers have individually been shown to predict outcomes in patients with HFrEF, the value of these over and above conventional clinical and laboratory variables, plus natriuretic peptides, is uncertain. Purpose To test the incremental predictive value of 11 novel biomarkers added to a recent prognostic model...

Background Anaemia is common in patients with HFrEF and is associated with poor clinical outcomes. Although they reduce rates of mortality and heart failure hospitalization, renin-angiotensin (RAS) blockers lower haemoglobin and may induce anaemia. Concomitant neprilysin inhibition might ameliorate this effect of RAS blockers. Purpose We investiga...

Introduction Bilirubin is a recognized predictor of adverse outcomes in patients with heart failure and reduced ejection fraction (HFrEF), possibly because it is a marker of congestion. Alkaline phosphatase (ALP) is an enzyme produced in many tissues including the biliary ducts and elevated levels are also associated with congestion. Purpose To ex...

Background Treatment recommendations for heart failure (HF) with reduced ejection fraction are primarily centered on New York Heart Association (NYHA) classification, such that apparently asymptomatic patients might not be eligible for disease-modifying therapies. NYHA classification, however, may be particularly limited to discriminate mild forms...

Background and Aims Patients with heart failure with reduced ejection fraction (HFrEF) are at significant risk of stroke. Anticoagulation reduces this risk in patients with and without atrial fibrillation (AF), but the risk-to-benefit balance in the latter group, overall, is not favourable. Identification of patients with HFrEF, without AF, at the...

Background Compared with enalapril, sacubitril/valsartan lowered HbA1c and reduced new insulin therapy in patients with heart failure with reduced ejection fraction (HFrEF) and diabetes in the PARADIGM-HF trial. We sought to assess the glycemic effects of sacubitril/valsartan in heart failure with preserved ejection fraction (HFpEF) and diabetes, a...

Aims We aimed to assess the value of GDF-15, a stress-responsive cytokine, in predicting clinical outcomes in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and anemia Methods and results Serum GDF-15 was assessed in 1582 HFrEF and mild-to-moderate anemia patients who where followed for 28 months in the Reduction of Events...

Objectives The aim of this study was to examine outcomes in patients with heart failure with reduced ejection fraction (HFrEF) not taking diuretic medications and after diuretic medications are started. Background Up to 20% of patients in HFrEF trials are not taking diuretic agents at baseline, but little is known about them. Methods Patient char...

Background Sick leave due to common mental disorders (CMDs) is a public health problem in several countries, including Sweden. Given that symptom relief does not necessarily correspond to return to work, health care interventions focusing on factors that have proven important to influence the return to work process, such as self-efficacy, are warra...

In healthcare systems patient engagement and care satisfaction are less than optimal. Different solutions have been proposed to recognise the patient in health care, including person-centred care. The University of Gothenburg Centre for Person-Centred Care (GPCC) steering committee formulated three ‘simple routines’ to initiate, integrate and safeg...

Aims Patients with heart failure are at higher risk of progression to end-stage renal disease (ESRD), regardless of ejection fraction (EF). We assessed the renal effects of angiotensin/neprilysin inhibition in a pooled anlaysis of 13 195 patients with heart failure with reduced and preserved EF. Methods and Results We combined data from PARADIGM-H...

Background Sudden death is a leading cause of mortality in HFrEF. In PARADIGM-HF, sacubitril/valsartan reduced the incidence of sudden death. The purpose of this post hoc study was to analyze the effect of sacubitril/valsartan, compared to enalapril, on the incidence of ventricular arrhythmias. Methods Adverse event reports related to ventricular...

Background Chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) are characterized by severe symptom burden and common acute worsening episodes that often require hospitalization and affect prognosis. Although many studies have shown that person-centered care (PCC) increases self-efficacy in patients with chronic conditions,...

Aims: Heart failure with reduced ejection fraction (HFrEF) and chronic obstructive pulmonary disease (COPD) individually cause significant morbidity and mortality. Their coexistence is associated with even worse outcomes, partly due to suboptimal heart failure therapy, especially underutilisation of beta-blockers. Our aim was to investigate outcom...

Background Sudden death (SD) and pump failure death (PFD) are leading modes of death in heart failure and preserved ejection fraction (HFpEF). Risk stratification for mode-specific death may aid in patient enrichment for new device trials in HFpEF. Methods Models were derived in 4116 patients in the Irbesartan in Heart Failure with Preserved Eject...

Background Loop diuretics are the mainstay of congestion treatment in patients with heart failure (HF). We assessed the association between baseline loop diuretic use and outcome. We also compared the increment in risk related to diuretic dose with conventional prognostic enrichment criteria used in the EMPHASIS-HF trial, which included patients wi...

Background Sudden death (SD) and pump failure death (PFD) are the two leading causes of death in patients with heart failure and reduced ejection fraction (HFrEF). Objective Identifying patients at higher risk for mode-specific death would allow better targeting of individual patients for relevant device and other therapies. Methods We developed...

Background Sacubitril/valsartan improves morbidity and mortality in patients with heart failure and reduced ejection fraction (HFrEF). Whether initiation of sacubitril/valsartan limits the use and dosing of other elements of guideline-directed medical therapy (GDMT) for HFrEF is unknown. We examined the effects of sacubitril/valsartan, compared wit...

BACKGROUND Sick leave due to common mental disorders (CMDs) is a public health problem in several countries, including Sweden. Given that symptom relief does not necessarily correspond to return to work, health care interventions focusing on factors that have proven important to influence the return to work process, such as self-efficacy, are warra...

Background Increasing healthcare costs need to be contained in order to maintain equality of access to care for all EU citizens. A cross‐disciplinary consortium of experts was supported by the EU FP7 research programme, to produce a roadmap on cost containment, while maintaining or improving the quality of healthcare. The roadmap comprises two driv...

Background Patients with heart failure with reduced ejection fraction (HFrEF) and insulin-treated diabetes have a high risk of cardiovascular complications. Mineralocorticoid receptor antagonists may mitigate this risk. We aim to explore the effect of eplerenone on cardiovascular outcomes and all-cause mortality in HFrEF patients with diabetes, inc...

The diagnosis of heart failure is classified in two main types depending on left ventricular ejection fraction usually by ejection fraction < or > 40%. The division has important implications for the treatment of heart failure Type 2 diabetes is an important and common co-morbidity in chronic heart failure. It makes the prognosis of heart failure w...

Background The incidence of pneumonia and subsequent outcomes has not been compared in patients with heart failure and reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). Objectives This study aimed to examine the rate and impact of pneumonia in the PARADIGM-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhib...

Background The net clinical benefit of cardiac disease-modifying drugs might be influenced by the interaction of different domains of disease burden. We assessed the relative contribution of cardiac, comorbid, and demographic factors in heart failure (HF) and how their interplay might influence HF prognosis and efficacy of sacubitril/valsartan acro...

Background: Person-Centered Care (PCC) is a promising approach towards improved quality of care and cost containment within health systems. It has been evaluated in Sweden and England. This feasibility study examines initial PCC implementation in a rehabilitation hospital for children in Poland. Methods: The WE-CARE Roadmap of enablers was used...

Aims: Prognostic models of sudden cardiac death (SCD) typically incorporate data at only a single time-point. We investigated independent predictors of SCD addressing the impact of integrating time-varying covariates to improve prediction assessment. Methods and results: We studied 8,399 patients enrolled in the PARADIGM-HF trial and identified...

Background : N-terminal pro-B-type natriuretic peptide (NTproBNP) plasma concentrations are independent prognostic markers in patients with heart failure with reduced ejection fraction (HFrEF). Whether a differential risk association between NTproBNP plasma concentrations and risk of cardiovascular (CV) versus non-CV adverse events exists is not we...

Background Chronic obstructive pulmonary disease (COPD) is a common comorbidity in heart failure with reduced ejection fraction, associated with undertreatment and worse outcomes. New treatments for heart failure with reduced ejection fraction may be particularly important in patients with concomitant COPD. Methods and Results We examined outcomes...

BACKGROUND Chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) are characterized by severe symptom burden and common acute worsening episodes that often require hospitalization and affect prognosis. Although many studies have shown that person-centered care (PCC) increases self-efficacy in patients with chronic conditions,...

Aim To evaluate the effects of PCC in the form of structured telephone support on self‐reported cardiac self‐efficacy in patients with COPD. Methods We enrolled 105 patients, aged ≥50 years, admitted to hospital and diagnosed with COPD from January 2015 to November 2016. The patients received usual care or PCC via telephone added to usual care. Th...

Aims Little is known about patient characteristics, outcomes, and the effect of treatment in relation to duration of heart failure (HF). We have investigated these questions in PARADIGM‐HF. The aim of the study was to compare patient characteristics, outcomes, and the effect of sacubitril/valsartan, compared with enalapril, in relation to time from...

Objectives: The purpose of this study was to investigate the effect of sacubitril/valsartan therapy on sudden cardiac death (SCD) according to the use of and eligibility for an implantable cardioverter-defibrillator (ICD), stratified by heart failure cause. Background: SCD still accounts for a significant proportion of overall mortality in heart...

Introduction The number of people dealing with common mental disorders (CMDs) is a major concern in many countries, including Sweden. Sickness absence resulting from CMDs is often long-lasting and advancing return to work is a complex process impacted by several factors, among which self-efficacy appears to be an important personal resource. Person...

Aims The importance of intraventricular conduction delay (IVCD), incidence of new IVCD and its relationship to outcomes in heart failure and reduced ejection fraction (HFrEF) is not well studied. We addressed these questions in the PARADIGM‐HF and ATMOSPHERE trials. Methods and Results Risk of the primary composite outcome of cardiovascular death...

Background A core feature of chronic obstructive pulmonary disorder (COPD) and chronic heart failure (CHF) is that symptoms may change rapidly because of illness progression. Thus, these chronic conditions are associated with high rehospitalisation rates. Person-centred care (PCC) has been shown to have several benefits for patients with COPD or CH...

Aims The prevalence of liver function abnormalities is common in patients with heart failure (HF) with reduced ejection fraction (HFrEF). We assessed the impact of liver function on prognosis and the effect of sacubitril/valsartan on measures of liver function in patients with HFrEF. Methods and results The PARADIGM‐HF trial was a randomized, doub...

Objectives The authors investigated the relationship between past or incident myocardial infarction (MI) and cardiovascular (CV) events in heart failure with preserved ejection fraction (HFpEF). Background MI and HFpEF share some common risk factors. The prognostic significance of MI in patients with HFpEF is uncertain. Methods The authors pooled...

Aims Frailty, characterized by loss of homeostatic reserves and increased vulnerability to physiological decompensation, results from an aggregation of insults across multiple organ systems. Frailty can be quantified by counting the number of ‘health deficits’ across a range of domains. We assessed the frequency of, and outcomes related to, frailty...

Background: Both BNP (B-type natriuretic peptide) and NT-proBNP (N-terminal pro B-type natriuretic peptide) are widely used to aid diagnosis, assess the effect of therapy, and predict outcomes in heart failure and reduced ejection fraction. However, little is known about how these 2 peptides compare in heart failure and reduced ejection fraction,...

Importance Accurate prediction of risk of death or hospitalizations in patients with heart failure (HF) may allow physicians to explore how more accurate decisions regarding appropriateness and timing of disease-modifying treatments, advanced therapies, or the need for end-of-life care can be made. Objective To develop and validate a prognostic mo...

Background: To assess the prognostic value of mineralocorticoid receptor antagonist (MRA) initiation and change in serum potassium (K+ ) during follow-up in patients post-acute myocardial infarction with left ventricular dysfunction or chronic heart failure (HF) and reduced ejection fraction (HFrEF). Methods and results: Risk scores for predicti...

Background: To describe characteristics and outcomes in women and men with heart failure with preserved ejection fraction. Methods: Baseline characteristics (including biomarkers and quality of life) and outcomes (primary outcome: composite of first heart failure hospitalization or cardiovascular death) were compared in 4458 women and 4010 men e...

Aims: To investigate the relationship between heart rate and outcomes in heart failure and reduced ejection fraction (HFrEF) patients in sinus rhythm (SR) and atrial fibrillation (AF) adjusting for natriuretic peptide concentration, a powerful prognosticator. Methods and results: Of 13 562 patients from two large HFrEF trials, 10 113 (74.6%) wer...

Introduction Fatigue is a prevalent symptom that is associated with various conditions. In patients with chronic heart failure (CHF), fatigue is one of the most commonly reported and distressing symptoms and it is associated with disease progression. Person-centred care (PCC) is a fruitful approach to increase the patient’s ability to handle their...

Background: While disease-modifying therapies exist for heart failure (HF) with reduced left ventricular ejection fraction (LVEF), few options are available for patients in the higher range of LVEF (>40%). Sacubitril/valsartan has been compared with a renin-angiotensin-aldosterone-system inhibitor alone in 2 similarly designed clinical trials of p...

Aims: Ivabradine has been approved in heart failure with reduced ejection fraction (HFrEF) and elevated heart rate despite guideline-directed medical therapy (GDMT) to reduce cardiovascular (CV) death and hospitalization for worsening HF. The median value of 77 b.p.m. is the lower bound selected for the regulatory approval in Canada, South Africa,...

Background: Visit-to-visit office blood pressure (BP) variability (BPV) has been associated with morbidity and mortality outcomes in several cardiovascular conditions. The aim of this study was to evaluate the association between BPV and outcomes in patients with heart failure and reduced ejection fraction and the effect of eplerenone on BPV. Met...

Background: The contemporary prognostic value of the physical examination- beyond traditional risk factors including natriuretic peptides, risk scores, and symptoms-in heart failure (HF) with reduced ejection fraction is unknown. We aimed to determine the association between physical signs of congestion at baseline and during study follow-up with...

Background: Although heart failure with preserved ejection fraction (HFpEF) is considered a disease of the elderly, younger patients are not spared from this syndrome. Objectives: This study therefore investigated the associations among age, clinical characteristics, and outcomes in patients with HFpEF. Methods: Using data on patients with lef...

Background Myocardial infarction (MI) and heart failure with preserved ejection fraction (HFpEF) share common risk factors. Little is known about the prognostic significance of remote or recent MI in patients with HFpEF. Methods We pooled data from 3 trials: CHARM-Preserved, I-Preserve, and Americas region of TOPCAT (n=8,916), and examined whether...

Background Increased resting heart rate is a risk factor for cardiovascular mortality and morbidity. Mineralocorticoid receptor antagonists (MRAs) have been shown to improve cardiac sympathetic nerve activity, reduce heart rate and attenuate left ventricular remodelling. Whether or not the beneficial effects of MRA are affected by heart rate in hea...

Aims: Insulin causes sodium retention and hypoglycaemia and its use is associated with worse outcomes in heart failure (HF) with reduced ejection fraction. We have investigated whether this is also the case in HF with preserved ejection fraction (HFpEF). Methods and results: We examined the association between diabetes/diabetes treatments and th...

OBJECTIVES The purpose of this study was to compare outcomes (and the effect of sacubitril/valsartan) according to etiology in the PARADIGM-HF (Prospective comparison of angiotensin-receptor-neprilysin inhibitor [ARNI] with angio- tensin-converting-enzyme inhibitor [ACEI] to Determine Impact on Global Mortality and morbidity in Heart Failure) trial...

Objectives This study examined the relationship between prior pacemaker implantation and clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF). Background Conventional right ventricular pacing causes electrical and mechanical left ventricular dyssynchrony and may worsen left ventricular systolic dysfunction and...

Background Sodium–glucose co‐transporter 2 (SGLT2) inhibitors have been shown to reduce the risk of incident heart failure hospitalization in individuals with type 2 diabetes who have, or are at high risk of, cardiovascular disease. Most patients in these trials did not have heart failure at baseline and the effect of SGLT2 inhibitors on outcomes i...

Background Costs associated with an ACS incident are most pronounced in the acute phase but are also considerably long after the initial hospitalisation, partly due to considerable productivity losses, which constitute a substantial part of the economic burden of the disease. Studies suggest that person-centred care may improve health-related quali...

Background: Natriuretic peptides are substrates of neprilysin; hence, B-type natriuretic peptide (BNP) concentrations rise with neprilysin inhibition. Thus, the clinical validity of measuring BNP in sacubitril/valsartan-treated patients has been questioned, and use of N-terminal pro-B-type natriuretic peptides (NT-proBNP) has been preferred and re...

Background: Myocardial fibrosis is an important pathophysiological mechanism underlying the development of heart failure (HF). Given the biochemical targets of sacubitril/valsartan, we hypothesized that circulating biomarkers reflecting the mechanisms that determine extracellular matrix (ECM) homeostasis, including collagen synthesis, processing,...

OBJECTIVES This study examined the relationship between income inequality and heart failure outcomes. BACKGROUND The income inequality hypothesis postulates that population health is influenced by income distribution within a society, with greater inequality associated with worse outcomes. METHODS This study analyzed heart failure outcomes in 2 lar...

Aims To assess differences in diuretic dose requirements in patients treated with sacubitril/valsartan compared with enalapril in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM‐HF) trial. Methods and results Overall, 8399 patients with New York Heart Association class I...

Background: Heart failure (HF) trials initiated in the last century highlighted many differences between men and women. Of particular concern was undertreatment of women compared with men, but much has changed during the past 20 years. Objectives: This study sought to identify these changes, which may give a new perspective on the management of,...

Aims Nearly 60% of the world's population lives in Asia but little is known about the characteristics and outcomes of Asian patients with heart failure with reduced ejection fraction (HFrEF) compared to other areas of the world. Methods and results We pooled two, large, global trials, with similar design, in 13 174 patients with HFrEF (patient dis...

Aims We examined the prognostic importance of N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) and troponin T (TnT) in heart failure patients with and without diabetes. Methods and results We measured NT‐proBNP and TnT in the biomarker substudy of the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidi...

Importance The addition of neprilysin inhibition to standard therapy, including a renin-angiotensin system blocker, has been demonstrated to improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF) compared with standard therapy alone. The long-term absolute risk reduction from angiotensin receptor neprilysin inhibitor...

The current study operationalized, assessed, and evaluated the feasibility and preliminary effects of implementing a person-centered approach to incontinence care for older adults with cognitive decline in residential care facilities (RCFs) in Sweden. Twenty health care workers were purposively sampled from two intervention RCFs. Process outcome wa...

Aims Growth differentiation factor‐15 (GDF‐15) is associated with adverse prognosis in cardiovascular (CV) and non‐CV diseases. We evaluated the association of GDF‐15 with CV and non‐CV outcomes in the PARADIGM‐HF trial. Methods and results In 1935 patients with heart failure and reduced ejection fraction (HFrEF) in PARADIGM‐HF, median GDF‐15 valu...

To evaluate the effects of person-centred support via telephone in two chronically ill patient groups, chronic obstructive pulmonary disease (COPD) and/or chronic heart failure (CHF).221 patients ≥ 50 years with COPD and/or CHF were randomized to usual care vs. usual care plus a person-centred telephone-support intervention and followed for six mon...

Background: Long term health conditions, including chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD), are one of the major challenges facing healthcare systems worldwide; and telehealth has been suggested as a safe option to promote self­management. The effectiveness of person­ centred care as a tool to improve health car...

Importance: Health-related quality of life (HRQL) of patients with heart failure is markedly reduced compared with that in patients with other chronic diseases, demonstrating substantial limitations in physical and social activities. In the Prospective Comparison of ARNI With an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity i...

Background: In PARADIGM-HF (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure), heart failure treatment with sacubitril/valsartan reduced the primary composite outcome of cardiovascular death or heart failure hospit...

Patients with chronic heart failure with reduced ejection fraction (HFrEF) benefit from medical and device therapies targeting sudden cardiac death (SCD). Contemporary estimates of SCD risk after hospitalization for HF are limited. We describe the incidence, timing, and clinical predictors of SCD following hospitalization for HFrEF (≤40%) in the EV...

Objectives: The purpose of this study was to evaluate the renal effects of sacubitril/valsartan in patients with heart failure and reduced ejection fraction. Background: Renal function is frequently impaired in patients with heart failure with reduced ejection fraction and may deteriorate further after blockade of the renin-angiotensin system....

Background: The lack of reliable predictors of the efficacy of drugs and devices in heart failure (HF) has presented a major hurdle to the development and evaluation of novel therapies. Objectives: To determine whether treatment-related changes in natriuretic peptides (NP) predict longer-term therapeutic effects in clinical trials of HF. Method...