Publications by authors named "Lars H Lund"

309 Publications

Generalizability of HFA-PEFF and HFPEF Diagnostic Algorithms and Associations with Heart Failure Indices and Proteomic Biomarkers: Insights from PROMIS-HFpEF.

J Card Fail 2021 Feb 26. Epub 2021 Feb 26.

Department of Medicine, Cardiology Unit, Karolinska Institutet, Stockholm, Sweden.

Background: Diagnosing heart failure with preserved ejection fraction (HFpEF) remains challenging. We aimed to evaluate the generalizability of the HFA-PEFF and HFPEF diagnostic algorithms and associations with HF severity, coronary microvascular dysfunction and proteomic biomarkers.

Methods: Diagnostic likelihood of HFpEF was calculated in the prospective, multinational PROMIS-HFpEF (Prevalence of microvascular dysfunction in HFpEF) cohort employing current ESC recommendations, HFA-PEFF and HFPEF algorithms. Associations between the two algorithms and left atrial (LA) function, Doppler-based coronary flow reserve (CFR), 6-minute walk test (6MWT), QoL and proteomic biomarkers were investigated.

Results: Of 181 subjects with EF ≥ 50%, 129 (71%) and 94 (52%) fulfilled criteria for high-likelihood HFpEF as per HFA-PEFF and HFPEF, while 28 and 46% were classified as intermediate-likelihood, requiring additional hemodynamic testing. High-likelihood HFpEF subjects were older with higher prevalence of atrial fibrillation and lower global longitudinal strain (GLS) and LA reservoir strain (p < 0.001 for all variables). LA reservoir strain and GLS were inversely associated with both HFA-PEFF and HFPEF scores (TauB =-0.35 and -0.46 and -0.21 and -0.31, p<0.001 for all). There were no associations between scoring and 6MWT, QoL and CFR. Both scores were associated with biomarkers related to inflammation, oxidative stress, and fibrosis.

Conclusions: While the HFA-PEFF and HFPEF scores were associated with measures of HF severity and biomarkers related to HFpEF, they demonstrated modest and differential ability to identify HFpEF noninvasively, necessitating additional functional testing to confirm diagnosis.
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http://dx.doi.org/10.1016/j.cardfail.2021.02.005DOI Listing
February 2021

Mechanistic and Therapeutic Implications of Extracellular Vesicles as a Potential Link Between Covid-19 and Cardiovascular Disease Manifestations.

Front Cell Dev Biol 2021 11;9:640723. Epub 2021 Feb 11.

Department of Medicine, Cardiology Research Unit, Karolinska Institutet, Stockholm, Sweden.

Extracellular vesicles (EVs), which are cell released double layered membrane particles, have been found in every circulating body fluid, and provide a tool for conveying diverse information between cells, influencing both physiological and pathological conditions. Viruses can hijack the EVs secretory pathway to exit infected cells and use EVs endocytic routes to enter uninfected cells, suggesting that EVs and viruses can share common cell entry and biogenesis mechanisms. SARS-CoV-2 is responsible of the coronavirus disease 2019 (Covid-19), which may be accompanied by severe multi-organ manifestations. EVs may contribute to virus spreading via transfer of virus docking receptors such as CD9 and ACE2. Covid-19 is known to affect the renin angiotensin system (RAS), and could promote secretion of harmful EVs. In this scenario EVs might be linked to cardiovascular manifestations of the Covid-19 disease through unbalance in RAS. In contrast EVs derived from mesenchymal stem cells or cardiosphere derived cells, may promote cardiovascular function due to their beneficial effect on angiogenesis, fibrosis, contractility and immuno-modulation. In this article we assessed the potential impact of EVs in cardiovascular manifestations of Covid-19 and highlight potential strategies to control the extracellular signaling for future therapies.
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http://dx.doi.org/10.3389/fcell.2021.640723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905102PMC
February 2021

The Heart Failure Association Atlas: Heart Failure Epidemiology and Management Statistics 2019.

Eur J Heart Fail 2021 Feb 26. Epub 2021 Feb 26.

Centre of Clinical and Experimental Medicine, IRCCS San Raffaele Pisana, Rome, Italy.

Aims: The Heart Failure Association (HFA) of the European Society of Cardiology (ESC) developed the HFA Atlas to provide a contemporary description of heart failure (HF) epidemiology, resources, reimbursement of guideline-directed medical therapy (GDMT) and activities of the National Heart Failure Societies (NHFS) in ESC member countries.

Methods And Results: The HFA Atlas Survey was conducted in 2018-2019 in 42 ESC countries. The quality and completeness of source data varied across countries. The median incidence of HF was 3.20 (interquartile range (IQR), 2.66-4.17) cases per 1000 person-years, ranging from ≤2 in Italy and Denmark to >6 in Germany. The median HF prevalence was 17.20 (IQR, 14.30-21) cases per 1000 people, ranging from ≤12 in Greece and Spain to >30 in Lithuania and Germany. The median number of HF hospitalisations was 2,671 (IQR, 1,771-4,317) per million people annually, ranging from <1,000 in Latvia and North Macedonia, to >6,000 in Romania, Germany and Norway. The median length of hospital stay for an admission with HF was 8.50 (IQR, 7.38-10) days. Diagnostic and management resources for HF varied, with high-income ESC member countries having substantially more resources compared with middle-income countries. The median number of hospitals with dedicated HF centres was 1.16 (IQR, 0.51-2.97) per million people, ranging from <0.10 in Russian Federation and Ukraine to >7 in Norway and Italy. Nearly all countries reported full or partial reimbursement of standard GDMT, except ivabradine and sacubitril/valsartan. Almost all countries reported having NHFS working groups and nearly half had HF patient organisations.

Conclusions: The first report from the HFA Atlas has shown considerable heterogeneity in HF disease burden, the resources available for its management and data quality across ESC member countries. The findings emphasise the need for a systematic approach to the capture of HF statistics so that inequalities and improvements in care may be quantified and addressed. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/ejhf.2143DOI Listing
February 2021

Use of Sodium-Glucose Co-transporter 2 Inhibitors in Patients with Heart Failure and Type 2 Diabetes Mellitus: Data from the Swedish Heart Failure Registry.

Eur J Heart Fail 2021 Feb 18. Epub 2021 Feb 18.

Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

Aims: Use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in real-world heart failure (HF) is poorly characterised. In contemporary patients with HF and type 2 diabetes (T2DM) we assessed overtime SGLT2i use, clinical characteristics and outcomes associated with SGLT2i use.

Methods And Results: T2DM patients enrolled in the Swedish HF Registry between 2016-2018 were considered. We performed multivariable logistic regression models to assess the independent predictors of SGLT2i use and Cox regression models in a 1:3 propensity score-matched cohort and relevant sub-groups to investigate the association between SGLT2i use and outcomes. Of 6805 eligible HF patients with T2DM, 376 (5.5%) received SGLT2i, whose use increased over time with 12% of patients on treatment at the end of 2018. Independent predictors of SGLT2i use were younger age, HF-specialty care, ischemic heart disease, preserved kidney function, and absent anaemia. Over a median follow-up of 256 days, SGLT2i use was associated with a 30% lower risk of CV death/first HF hospitalisation [hazard ratio (HR): 0.70 (95% confidence interval: 0.52-0.95)], which was consistent regardless of ejection fraction (EF), background metformin treatment and kidney function. SGLT2i use was also associated with lower risk of all-cause and CV death, HF and CV hospitalisation, and of CV death/myocardial infarction/stroke.

Conclusion: In a contemporary HF cohort with T2DM, SGLT2i use increased over time, was more common with specialist care, younger age, ischemic heart disease, and preserved renal function, and was associated with lower mortality and morbidity. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/ejhf.2131DOI Listing
February 2021

Association between renin-angiotensin-aldosterone system inhibitor use and COVID-19 hospitalization and death: a 1.4 million patient nationwide registry analysis.

Eur J Heart Fail 2020 Nov 22. Epub 2020 Nov 22.

Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

Aims: Renin-angiotensin-aldosterone system inhibitors (RAASi) improve outcomes in cardiorenal disease but concerns have been raised over increased risk of incident hospitalization and death from coronavirus disease 2019 (COVID-19). We investigated the association between use of angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs) or mineralocorticoid receptor antagonists (MRAs) and COVID-19 hospitalization/death in a large nationwide population.

Methods And Results: Patients with hypertension, heart failure, diabetes, kidney disease, or ischaemic heart disease registered in the Swedish National Patient Registry until 1 February 2020 were included and followed until 31 May 2020. COVID-19 cases were defined based on hospitalization/death for COVID-19. Multivariable logistic and Cox regressions were fitted to investigate the association between ACEi/ARB and MRA and risk of hospitalization/death for COVID-19 in the overall population, and of all-cause mortality in COVID-19 cases. We performed consistency analysis to quantify the impact of potential unmeasured confounding. Of 1 387 746 patients (60% receiving ACEi/ARB and 5.8% MRA), 7146 (0.51%) had incident hospitalization/death from COVID-19. After adjustment for 45 variables, ACEi/ARB use was associated with a reduced risk of hospitalization/death for COVID-19 (odds ratio 0.86, 95% confidence interval 0.81-0.91) in the overall population, and with reduced mortality in COVID-19 cases (hazard ratio 0.89, 95% confidence interval 0.82-0.96). MRA use was not associated with risk of any outcome. Consistency analysis showed that unmeasured confounding would need to be large for there to be harmful signals associated with RAASi use.

Conclusions: In a 1.4 million nationwide cohort, use of RAASi was not associated with increased risk of hospitalization for or death from COVID-19.
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http://dx.doi.org/10.1002/ejhf.2060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753665PMC
November 2020

Acknowledging the complex puzzle that links heart failure hospitalizations to outcomes. Letter regarding the article 'Readmission and death in patients admitted with new-onset versus worsening of chronic heart failure: insights from a nationwide cohort'.

Eur J Heart Fail 2020 Nov 22. Epub 2020 Nov 22.

Unit of Cardiology, Department of Medicine, Karolinska Institutet, and Heart and Vascular Theme, Karolinska University Hospital, Stockholm, Sweden.

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http://dx.doi.org/10.1002/ejhf.2061DOI Listing
November 2020

Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure.

N Engl J Med 2021 01 16;384(2):117-128. Epub 2020 Nov 16.

From Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston (D.L.B., C.P.C.); Colorado Prevention Center Clinical Research and Department of Medicine, Division of Cardiovascular Medicine, University of Colorado Anschutz Medical Campus, Aurora (M.S.); State University of New York Downstate School of Public Health, Brooklyn (M.S.); Université de Paris, French Alliance for Cardiovascular Trials, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, INSERM Unité 1148 (P.G.S.), and Paris Sorbonne University and Groupe Hospitalier Paris Saint Joseph (M.K.), Paris; Li Ka Shing Knowledge Institute (L.A.L., S.V.) and the Divisions of Endocrinology and Metabolism (L.A.L.) and Cardiac Surgery (S.V.), St. Michael's Hospital, and the Departments of Medicine and Nutritional Sciences (L.A.L) and Surgery and Pharmacology and Toxicology (S.V.), University of Toronto, Toronto; University of Texas Southwestern Medical Center and Parkland Health and Hospital System, Dallas (D.K.M.), and Lexicon Pharmaceuticals, The Woodlands (P.L.) - both in Texas; Vanderbilt University, Nashville (J.B.L.); the Division of Endocrinology, Diabetes, and Clinical Nutrition, Oregon Health and Science University, Portland (M.C.R.); University of Groningen-University Medical Center Groningen, Groningen, the Netherlands (A.A.V); Azienda Socio Sanitaria Territoriale Spedali Civili and University of Brescia, Brescia, Italy (M.M.); Karolinska Institutet, Stockholm (L.H.L.); Yale University, New Haven, CT (J.M.T.); Georgetown University, Washington, DC (C.S.W.); Wroclaw Medical University, Wroclaw, Poland (P.P.); Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (R.D.L.); and the University of Michigan, Ann Arbor (B.P.).

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure or death from cardiovascular causes among patients with stable heart failure. However, the safety and efficacy of SGLT2 inhibitors when initiated soon after an episode of decompensated heart failure are unknown.

Methods: We performed a multicenter, double-blind trial in which patients with type 2 diabetes mellitus who were recently hospitalized for worsening heart failure were randomly assigned to receive sotagliflozin or placebo. The primary end point was the total number of deaths from cardiovascular causes and hospitalizations and urgent visits for heart failure (first and subsequent events). The trial ended early because of loss of funding from the sponsor.

Results: A total of 1222 patients underwent randomization (608 to the sotagliflozin group and 614 to the placebo group) and were followed for a median of 9.0 months; the first dose of sotagliflozin or placebo was administered before discharge in 48.8% and a median of 2 days after discharge in 51.2%. Among these patients, 600 primary end-point events occurred (245 in the sotagliflozin group and 355 in the placebo group). The rate (the number of events per 100 patient-years) of primary end-point events was lower in the sotagliflozin group than in the placebo group (51.0 vs. 76.3; hazard ratio, 0.67; 95% confidence interval [CI], 0.52 to 0.85; P<0.001). The rate of death from cardiovascular causes was 10.6 in the sotagliflozin group and 12.5 in the placebo group (hazard ratio, 0.84; 95% CI, 0.58 to 1.22); the rate of death from any cause was 13.5 in the sotagliflozin group and 16.3 in the placebo group (hazard ratio, 0.82; 95% CI, 0.59 to 1.14). Diarrhea was more common with sotagliflozin than with placebo (6.1% vs. 3.4%), as was severe hypoglycemia (1.5% vs. 0.3%). The percentage of patients with hypotension was similar in the sotagliflozin group and the placebo group (6.0% and 4.6%, respectively), as was the percentage with acute kidney injury (4.1% and 4.4%, respectively). The benefits of sotagliflozin were consistent in the prespecified subgroups of patients stratified according to the timing of the first dose.

Conclusions: In patients with diabetes and recent worsening heart failure, sotagliflozin therapy, initiated before or shortly after discharge, resulted in a significantly lower total number of deaths from cardiovascular causes and hospitalizations and urgent visits for heart failure than placebo. (Funded by Sanofi and Lexicon Pharmaceuticals; SOLOIST-WHF ClinicalTrials.gov number, NCT03521934.).
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http://dx.doi.org/10.1056/NEJMoa2030183DOI Listing
January 2021

Optimized implementation of cardiac resynchronization therapy: a call for action for referral and optimization of care: A joint position statement from the Heart Failure Association (HFA), European Heart Rhythm Association (EHRA), and European Association of Cardiovascular Imaging (EACVI) of the European Society of Cardiology.

Eur J Heart Fail 2020 12;22(12):2349-2369

Cardiologie, CHU Rennes - LTSI Inserm UMR 1099, Université Rennes-1, Rennes, France.

Cardiac resynchronization therapy (CRT) is one of the most effective therapies for heart failure with reduced ejection fraction and leads to improved quality of life, reductions in heart failure hospitalization rates and all-cause mortality. Nevertheless, up to two-thirds of eligible patients are not referred for CRT. Furthermore, post-implantation follow-up is often fragmented and suboptimal, hampering the potential maximal treatment effect. This joint position statement from three European Society of Cardiology Associations, Heart Failure Association (HFA), European Heart Rhythm Association (EHRA) and European Association of Cardiovascular Imaging (EACVI), focuses on optimized implementation of CRT. We offer theoretical and practical strategies to achieve more comprehensive CRT referral and post-procedural care by focusing on four actionable domains: (i) overcoming CRT under-utilization, (ii) better understanding of pre-implant characteristics, (iii) abandoning the term 'non-response' and replacing this by the concept of disease modification, and (iv) implementing a dedicated post-implant CRT care pathway.
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http://dx.doi.org/10.1002/ejhf.2046DOI Listing
December 2020

Association Between β-Blocker Use and Mortality/Morbidity in Patients With Heart Failure With Reduced, Midrange, and Preserved Ejection Fraction and Advanced Chronic Kidney Disease.

Circ Heart Fail 2020 Nov 19;13(11):e007180. Epub 2020 Oct 19.

Department of Medical Epidemiology and Biostatistics (J.J.C.), Karolinska Institutet, Stockholm, Sweden.

Background: It is unknown if β-blockers reduce mortality/morbidity in patients with heart failure (HF) and advanced chronic kidney disease (CKD), a population underrepresented in HF trials.

Methods: Observational cohort of HF patients with advanced CKD (estimated glomerular filtration rate <30 mL/min per 1.73 m) from the Swedish Heart Failure Registry between 2001 and 2016. We first explored associations between β-blocker use, 5-year death, and the composite of cardiovascular death/HF hospitalization among 3775 patients with HF with reduced ejection fraction (HFrEF) and advanced CKD. We compared observed hazards with those from a control cohort of 15 346 patients with HFrEF and moderate CKD (estimated glomerular filtration rate <60-30 mL/min per 1.73 m), for whom β-blocker trials demonstrate benefit. Second, we explored outcomes associated to β-blocker among advanced CKD participants with preserved (HFpEF; N=2009) and midrange ejection fraction (HFmrEF; N=1514).

Results: During a median follow-up of 1.3 years, 2012 patients had a subsequent HF hospitalization, and 2849 died in the HFrEF cohort, of which 2016 died due to cardiovascular causes. Among patients with HFrEF, β-blocker use was associated with lower risk of death (adjusted hazard ratio 0.85 [95% CI, 0.75-0.96]) and cardiovascular mortality/HF hospitalization (0.87 [0.77-0.98]) compared with nonuse. The magnitude of the associations was similar to that observed for HFrEF patients with moderate CKD. Conversely, no significant association was observed for β-blocker users in advanced CKD with HFpEF (death: 0.88 [0.77-1.02], cardiovascular mortality/HF hospitalization: 1.05 [0.90-1.23]) or HFmrEF (death: 0.95 [0.79-1.14], cardiovascular mortality/HF hospitalization: 1.09 [0.90-1.31]).

Conclusions: In HFrEF patients with advanced CKD, the use of β-blockers was associated with lower morbidity and mortality. Although inconclusive due to limited power, these benefits were not observed in similar patients with HFpEF or HFmrEF.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007180DOI Listing
November 2020

Heart Failure Association of the European Society of Cardiology update on sodium-glucose co-transporter 2 inhibitors in heart failure.

Eur J Heart Fail 2020 11 27;22(11):1984-1986. Epub 2020 Oct 27.

Department of Medical Sciences, IRCCS San Raffaele Pisana, Rome, Italy.

The Heart Failure Association (HFA) of the European Society of Cardiology (ESC) has recently issued a position paper on the role of sodium-glucose co-transporter 2 (SGLT2) inhibitors in heart failure (HF). The present document provides an update of the position paper, based of new clinical trial evidence. Accordingly, the following recommendations are given: • Canagliflozin, dapagliflozin empagliflozin, or ertugliflozin are recommended for the prevention of HF hospitalization in patients with type 2 diabetes mellitus and established cardiovascular disease or at high cardiovascular risk. • Dapagliflozin or empagliflozin are recommended to reduce the combined risk of HF hospitalization and cardiovascular death in symptomatic patients with HF and reduced ejection fraction already receiving guideline-directed medical therapy regardless of the presence of type 2 diabetes mellitus.
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http://dx.doi.org/10.1002/ejhf.2026DOI Listing
November 2020

Congestion and Diuretic Resistance in Acute or Worsening Heart Failure.

Card Fail Rev 2020 Mar 28;6:e25. Epub 2020 Sep 28.

Karolinska Institutet, Department of Medicine, Stockholm, Sweden; and Karolinska University Hospital, Heart and Vascular Theme Stockholm, Sweden.

Hospitalisation for acute heart failure (AHF) is associated with high mortality and high rehospitalisation rates. In the absence of evidence-based therapy, treatment is aimed at stabilisation and symptom relief. The majority of AHF patients have signs and symptoms of fluid overload, and, therefore, decongestion is the number one treatment goal. Diuretics are the cornerstone of therapy in AHF, but the treatment effect is challenged by diuretic resistance and poor diuretic response throughout the spectrum of chronic to worsening to acute to post-worsening HF. Adequate dosing and monitoring and evaluation of diuretic effect are important for treatment success. Residual congestion at discharge is a strong predictor of worse outcomes. Therefore, achieving euvolaemia is crucial despite transient worsening renal function.
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http://dx.doi.org/10.15420/cfr.2019.18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539143PMC
March 2020

Proteomic Evaluation of the Comorbidity-Inflammation Paradigm in Heart Failure With Preserved Ejection Fraction: Results From the PROMIS-HFpEF Study.

Circulation 2020 Nov 9;142(21):2029-2044. Epub 2020 Oct 9.

Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (S.S.-v.W., L.B.-N., S.A.S., C.S., J.N., S.J.S.).

Background: A systemic proinflammatory state has been hypothesized to mediate the association between comorbidities and abnormal cardiac structure/function in heart failure with preserved ejection fraction (HFpEF). We conducted a proteomic analysis to investigate this paradigm.

Methods: In 228 patients with HFpEF from the multicenter PROMIS-HFpEF study (Prevalence of Microvascular Dysfunction in Heart Failure With Preserved Ejection Fraction), 248 unique circulating proteins were quantified by a multiplex immunoassay (Olink) and used to recapitulate systemic inflammation. In a deductive approach, we performed principal component analysis to summarize 47 proteins known a priori to be involved in inflammation. In an inductive approach, we performed unbiased weighted coexpression network analyses of all 248 proteins to identify clusters of proteins that overrepresented inflammatory pathways. We defined comorbidity burden as the sum of 8 common HFpEF comorbidities. We used multivariable linear regression and statistical mediation analyses to determine whether and to what extent inflammation mediates the association of comorbidity burden with abnormal cardiac structure/function in HFpEF. We also externally validated our findings in an independent cohort of 117 HFpEF cases and 30 comorbidity controls without heart failure.

Results: Comorbidity burden was associated with abnormal cardiac structure/function and with principal components/clusters of inflammation proteins. Systemic inflammation was also associated with increased mitral E velocity, E/e' ratio, and tricuspid regurgitation velocity; and worse right ventricular function (tricuspid annular plane systolic excursion and right ventricular free wall strain). Inflammation mediated the association between comorbidity burden and mitral E velocity (proportion mediated 19%-35%), E/e' ratio (18%-29%), tricuspid regurgitation velocity (27%-41%), and tricuspid annular plane systolic excursion (13%) (<0.05 for all), but not right ventricular free wall strain. TNFR1 (tumor necrosis factor receptor 1), UPAR (urokinase plasminogen activator receptor), IGFBP7 (insulin-like growth factor binding protein 7), and GDF-15 (growth differentiation factor-15) were the top individual proteins that mediated the relationship between comorbidity burden and echocardiographic parameters. In the validation cohort, inflammation was upregulated in HFpEF cases versus controls, and the most prominent inflammation protein cluster identified in PROMIS-HFpEF was also present in HFpEF cases (but not controls) in the validation cohort.

Conclusions: Proteins involved in inflammation form a conserved network in HFpEF across 2 independent cohorts and may mediate the association between comorbidity burden and echocardiographic indicators of worse hemodynamics and right ventricular dysfunction. These findings support the comorbidity-inflammation paradigm in HFpEF.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.045810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686082PMC
November 2020

Critical appraisal of the instantaneous end-diastolic pulmonary arterial wedge pressures.

ESC Heart Fail 2020 Oct 6. Epub 2020 Oct 6.

Centre for Fetal Medicine, Department of Obstetrics and Gynecology, Karolinska University Hospital, Stockholm, Sweden.

Aims: A substantial shift in the field of pulmonary hypertension (PH) is ongoing, as the previous practice of mean pulmonary arterial wedge pressure (PAWP ) is no longer supported. Instead, aiming for a better estimate of end-diastolic pressures (EDP), instantaneous PAWP at mid-A-wave (PAWP ) or, in the absence of an A-wave, at 130-160 ms following QRS onset has recently been recommended. Electrocardiogram-gated PAWP (PAWP ) has also been proposed. The quantitative differences as well as the diagnostic and prognostic utility of these novel PAWP measurements have not been evaluated. We set out to address these issues.

Methods And Results: Pressure tracings of 141 patients with PH due to left heart disease (PH-LHD) and 43 with primary pulmonary arterial hypertension (PAH) were analysed. PAWP was measured as follows: (i) mean pressure (PAWP ); (ii) per the latest consensus approach [PAWP , or in atrial fibrillation 130, 140, 150, and 160 ms following QRS onset (PAWP )]; (iii) at QRS onset (PAWP ); and (iv) Z-point (PAWP ). For each PAWP, the corresponding pulmonary vascular resistance (PVR) and diastolic pressure gradient were calculated. The cohort comprised 45% female. Mean age was 66 ± 15. PAWP was in good agreement with PAWP (17.3 [14.5 to 21.2] vs. 17.6 [14.2 to 21.6] mmHg, P = 0.63), whereas PAWP provided significantly lower values (15.3 [12.5 to 19.2] mmHg, P < 0.001). In atrial fibrillation, PAWP and PAWP yielded the optimal temporal and quantitative analyses of EDPs. The ability to differentiate PAH from PH-LHD was similar for the various PAWP measurements [PAWP : area under the curve (AUC) 0.98, confidence interval (CI) 0.96-0.99; PAWP : AUC 0.94, CI 0.91-0.98; PAWP : AUC 0.96, CI 0.94-0.99, P < 0.001 for all]. PVR based on instantaneous PAWP measurements failed to provide superior prognostic information in PH-LHD as compared with conventional PVR.

Conclusions: Although instantaneous PAWP measurement might better represent EDP, they nevertheless fail to yield incremental diagnostic or prognostic information in PH-LHD as compared with conventional measurements.
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http://dx.doi.org/10.1002/ehf2.13057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754752PMC
October 2020

Atrial fibrillation in heart failure with preserved ejection fraction: a risk marker, risk factor or confounder?

Heart 2020 Dec 5;106(24):1949. Epub 2020 Oct 5.

Unit of Cardiology, Department of Medicine, Karolinska Institutet, and Heart and Vascular Theme, Karolinska University Hospital, Stockholm, Sweden.

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http://dx.doi.org/10.1136/heartjnl-2020-317978DOI Listing
December 2020

Impact of Coronavirus Disease 2019 (COVID-19) Outbreak on Acute Admissions at the Emergency and Cardiology Departments Across Europe.

Am J Med 2020 Sep 30. Epub 2020 Sep 30.

Department of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland. Electronic address:

Purpose: We evaluated whether the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) pandemic was associated with changes in the pattern of acute cardiovascular admissions across European centers.

Methods: We set-up a multicenter, multinational, pan-European observational registry in 15 centers from 12 countries. All consecutive acute admissions to emergency departments and cardiology departments throughout a 1-month period during the COVID-19 outbreak were compared with an equivalent 1-month period in 2019. The acute admissions to cardiology departments were classified into 5 major categories: acute coronary syndrome, acute heart failure, arrhythmia, pulmonary embolism, and other.

Results: Data from 54,331 patients were collected and analyzed. Nine centers provided data on acute admissions to emergency departments comprising 50,384 patients: 20,226 in 2020 compared with 30,158 in 2019 (incidence rate ratio [IRR] with 95% confidence interval [95%CI]: 0.66 [0.58-0.76]). The risk of death at the emergency departments was higher in 2020 compared to 2019 (odds ratio [OR] with 95% CI: 4.1 [3.0-5.8], P < 0.0001). All 15 centers provided data on acute cardiology departments admissions: 3007 patients in 2020 and 4452 in 2019; IRR (95% CI): 0.68 (0.64-0.71). In 2020, there were fewer admissions with IRR (95% CI): acute coronary syndrome: 0.68 (0.63-0.73); acute heart failure: 0.65 (0.58-0.74); arrhythmia: 0.66 (0.60-0.72); and other: 0.68(0.62-0.76). We found a relatively higher percentage of pulmonary embolism admissions in 2020: odds ratio (95% CI): 1.5 (1.1-2.1), P = 0.02. Among patients with acute coronary syndrome, there were fewer admissions with unstable angina: 0.79 (0.66-0.94); non-ST segment elevation myocardial infarction: 0.56 (0.50-0.64); and ST-segment elevation myocardial infarction: 0.78 (0.68-0.89).

Conclusion: In the European centers during the COVID-19 outbreak, there were fewer acute cardiovascular admissions. Also, fewer patients were admitted to the emergency departments with 4 times higher death risk at the emergency departments.
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http://dx.doi.org/10.1016/j.amjmed.2020.08.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526639PMC
September 2020

The Differential Impact of the Left Atrial Pressure Components on Pulmonary Arterial Compliance-Resistance Relationship in Heart Failure.

J Card Fail 2021 Mar 18;27(3):277-285. Epub 2020 Sep 18.

Department of Medicine, Karolinska Institute, Stockholm, Sweden; Heart and Vascular Theme, Karolinska University Hospital, Stockholm, Sweden. Electronic address:

Background: An increase in the pulmonary capillary wedge pressure (PAWP) has been shown to impact on the inherent relationship between the pulmonary arterial compliance (PAC) and pulmonary vascular resistance (PVR), thus augmenting the pulsatile relative to the resistive load of the right ventricle. However, the PAWP comprises the integration of both the steady and the pulsatile pressure components. We sought to address the differential impact of the these distinct PAWP components on the PAC-PVR relationship in a cohort of patients with heart failure.

Methods And Results: The study population consisted of 192 patients with hemodynamic findings diagnostic for heart failure. Off-line analysis was performed using the MATLAB software. The steady and pulsatile PAWP components were calculated as mid-A pressure and mean pressure during the V-wave oscillation, respectively. The PAC and PVR were hyperbolically and inversely associated and the subgroup of patients with PAWP above the median (>18 mm Hg) displayed a significant left and downward shift of the curve fit (P < .001). The shift in the PAC-PVR fit between patients with higher versus low steady PAWP was not significant (P = .43). In contrast, there was a significant downward and leftward shift of the PVR-PAC curve fit for the subgroup with a higher pulsatile PAWP (P < .001). Furthermore, only the pulsatile PAWP was significantly associated with the time-constant of the pulmonary circulation, assessed as the PAC × PVR product (P < .001).

Conclusions: In patients with heart failure, the pulsatile rather than the steady PAWP component stands for the previously documented shift of the PAC-PVR relationship occurring at an elevated PAWP.
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http://dx.doi.org/10.1016/j.cardfail.2020.09.008DOI Listing
March 2021

Self-care of heart failure patients: practical management recommendations from the Heart Failure Association of the European Society of Cardiology.

Eur J Heart Fail 2020 Sep 18. Epub 2020 Sep 18.

Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.

Self-care is essential in the long-term management of chronic heart failure. Heart failure guidelines stress the importance of patient education on treatment adherence, lifestyle changes, symptom monitoring and adequate response to possible deterioration. Self-care is related to medical and person-centred outcomes in patients with heart failure such as better quality of life as well as lower mortality and readmission rates. Although guidelines give general direction for self-care advice, health care professionals working with patients with heart failure need more specific recommendations. The aim of the management recommendations in this paper is to provide practical advice for health professionals delivering care to patients with heart failure. Recommendations for nutrition, physical activity, medication adherence, psychological status, sleep, leisure and travel, smoking, immunization and preventing infections, symptom monitoring, and symptom management are consistent with information from guidelines, expert consensus documents, recent evidence and expert opinion.
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http://dx.doi.org/10.1002/ejhf.2008DOI Listing
September 2020

Diagnostic utility of right atrial reservoir strain to identify elevated right atrial pressure in heart failure.

Int J Cardiol 2021 Feb 14;324:227-232. Epub 2020 Sep 14.

Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Heart and Vascular Theme, Karolinska University Hospital, Stockholm, Sweden. Electronic address:

Background: Accurate non-invasive estimation of right atrial pressure (RAP) is essential to assess volume status and optimize therapy in heart failure (HF). This study aimed to evaluate the utility of right atrial reservoir strain (RASr) assessed by speckle-tracking echocardiography to identify elevated RAP in HF and compare diagnostic performance with estimated RAP employing inferior vena cava size and collapsibility (RAP), in addition to RA area.

Method: Association between RASr and invasive RAP (RAP) was examined in 103 HF subjects that underwent standard echocardiography with speckle-tracking strain analysis directly followed by right heart catheterization. The discriminatory ability of RASr to identify RAP > 7 mmHg was evaluated and compared with RAP and RA area.

Results: RASr demonstrated association with RAP (β = -0.41, p < 0.001) and was an independent predictor when adjusted for potential confounders (β = -0.25, p < 0.001). Further, RASr showcased strong discriminatory ability to identify subjects with RAP > 7 mmHg (AUC = 0.78; 95% CI 0.68-0.87; p < 0.001). At a cut-off value of -15%, RASr displayed 78% sensitivity and 72% specificity to identify elevated RAP In comparison, RAP (AUC = 0.71; 95% CI 0.61-0.81; p < 0.001) demonstrated 89% sensitivity and 32% specificity with high false positive rate. RA area (AUC = 0.66; 95% CI 0.55-0.76, p = 0.005) displayed 64% sensitivity and 53% specificity.

Conclusions: RASr demonstrates good ability to identify elevated RAP and relatively stronger diagnostic performance when compared with conventional non-invasive measures. RASr may be useful as a novel noninvasive estimate of RAP in HF management.
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http://dx.doi.org/10.1016/j.ijcard.2020.09.008DOI Listing
February 2021

Non-insulin antihyperglycaemic drugs and heart failure: an overview of current evidence from randomized controlled trials.

ESC Heart Fail 2020 Sep 10. Epub 2020 Sep 10.

Department of Medicine, University of Mississippi, Jackson, MS, USA.

Type 2 diabetes mellitus (T2DM) is highly prevalent in the general population and especially in patients with heart failure (HF). It is not only a risk factor for incident HF, but is also associated with worse outcomes in prevalent HF. Therefore, antihyperglycaemic management in patients at risk of or with established HF is of importance to reduce morbidity/mortality. Following revision of the drug approval process in 2008 by the Food and Drug Administration and European Medicines Agency, several cardiovascular outcome trials on antihyperglycaemic drugs have recently investigated HF endpoints. Signals of harm in terms of increased risk of HF have been identified for thiazolidinediones and the dipeptidyl peptidase 4 inhibitor saxagliptin, and therefore, these drugs are not currently recommended in HF. Sulfonylureas also have an unfavourable safety profile and should be avoided in patients at increased risk of/with HF. Observational studies have assessed the use of metformin in patients with HF, showing potential safety and potential survival/morbidity benefits. Overall use of glucagon-like peptide 1 receptor agonists has not been linked with any clear benefit in terms of HF outcomes. Sodium-glucose cotransporter protein 2 inhibitors (SGLT2i) have consistently shown to reduce risk of HF-related outcomes in T2DM with and without HF and are thus currently recommended to lower risk of HF hospitalization in T2DM. Recent findings from the DAPA-HF trial support the use of dapagliflozin in patients with HF with reduced ejection fraction and, should ongoing trials with empagliflozin, sotagliflozin, and canagliflozin prove efficacy, will pave the way for SGLT2i as HF treatment regardless of T2DM.
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http://dx.doi.org/10.1002/ehf2.12937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755024PMC
September 2020

If it ain't broken, don't fix it (but if it is, make sure you know): aortic valve interventions during left ventricular assist device implantation.

Eur J Heart Fail 2020 10 28;22(10):1888-1890. Epub 2020 Sep 28.

Cardiology, ASST Spedali Civili, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.

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http://dx.doi.org/10.1002/ejhf.1997DOI Listing
October 2020

Implementation of sacubitril/valsartan in Sweden: clinical characteristics, titration patterns, and determinants.

ESC Heart Fail 2020 Sep 3. Epub 2020 Sep 3.

Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

Aims: The aim of this study is to study the introduction of sacubitril/valsartan (sac/val) in Sweden with regards to regional differences, clinical characteristics, titration patterns, and determinants of use and discontinuation.

Methods And Results: A national cohort of heart failure was defined from the Swedish Prescribed Drug Register and National Patient Register. A subcohort with additional data from the Swedish Heart Failure Registry (SwedeHF) was also studied. Cohorts were subdivided as per sac/val prescription and registration in SwedeHF. Median sac/val prescription rate was 20 per 100 000 inhabitants. Between April 2016 and December 2017, we identified 2037 patients with ≥1 sac/val prescription, of which 1144 (56%) were registered in SwedeHF. Overall, patients prescribed with sac/val were younger, more frequently male, and had less prior cardiovascular disease than non-sac/val patients. In SwedeHF subcohort, patients prescribed with sac/val had lower ejection fraction. Overall, younger age [hazard ratio 2.81 (95% confidence interval 2.45-3.22)], registration in SwedeHF [1.97 (1.83-2.12)], male gender [1.50 (1.37-1.64)], ischaemic heart disease [1.50 (1.39-1.62)], lower left ventricular ejection fraction [3.06 (2.18-4.31)], and New York Heart Association IV [1.50 (1.22-1.84)] were predictors for sac/val use. As initiation dose in the sac/val cohort, 38% received 24/26 mg, 54% 49/51 mg, and 9% 97/103 mg. Up-titration to the target dose was achieved in 57% of the overall cohort over a median follow-up of 6 months. The estimated treatment persistence for any dose at 360 days was 82%.

Conclusions: Implementation of sac/val in Sweden was slow and varied five-fold across different regions; younger age, male, SwedeHF registration, and ischaemic heart disease were among the independent predictors of receiving sac/val. Overall, treatment persistence and tolerability was high.
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http://dx.doi.org/10.1002/ehf2.12883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754959PMC
September 2020

Association of Coronary Microvascular Dysfunction With Heart Failure Hospitalizations and Mortality in Heart Failure With Preserved Ejection Fraction: A Follow-up in the PROMIS-HFpEF Study.

J Card Fail 2020 Nov 23;26(11):1016-1021. Epub 2020 Aug 23.

Department of Medicine, Cardiology Unit, Karolinska Institutet, Stockholm, Sweden; Karolinska University hospital, Heart, Vascular and Neuro Theme, Karolinska University hospital, Stockholm, Sweden.

Background: Coronary microvascular dysfunction (CMD) is common in heart failure with preserved ejection fraction (HFpEF). We assessed the association of CMD with hospitalization and mortality in HFpEF.

Methods And Results: We assessed the 1-year outcomes in patients from the PROMIS-HFpEF study, a prospective observational study of patients with chronic stable HFpEF undergoing coronary flow reserve measurements. Outcomes were (1) time to cardiovascular (CV) death/first HF hospitalization, (2) CV death/recurrent HF hospitalizations, (3) all-cause death/first HF hospitalization, and (4) first and (5) recurrent all-cause hospitalizations. CMD was defined as coronary flow reserve of <2.5. Time to CV death/first hospitalization was compared by log-rank test and recurrent HF and all-cause hospitalizations by Poisson test. Of 263 patients enrolled, 257 were evaluable at 1 year. Where the coronary flow reserve was interpretable (n = 201), CMD was present in 150 (75%). The median follow-up was 388 days (Q1, Q3 365, 418). The outcome of CV death/first HF hospitalization occurred in 15 patients (4 CV deaths). The incidence rate was in CMD 96 per 1000 person-years, 95% confidence interval 54-159, vs non-CMD 0 per1000 person-years, 95% confidence interval 0-68, P = .023, and remained significant after accounting for selected clinical variables. In patients with CMD, the incidence rates were significantly higher also for CV death/recurrent HF hospitalizations, all-cause death/first HF, and recurrent but not first all-cause hospitalization.

Conclusions: In this exploratory assessment of the prognostic role of CMD in HFpEF, CMD was independently associated with primarily CV- and HF-specific events. The high prevalence of CMD and its CV and HF specific prognostic role suggest CMD may be a potential treatment target in HFpEF.
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http://dx.doi.org/10.1016/j.cardfail.2020.08.010DOI Listing
November 2020

Hyperglycemia Induces Myocardial Dysfunction via Epigenetic Regulation of JunD.

Circ Res 2020 Oct 20;127(10):1261-1273. Epub 2020 Aug 20.

Cardiology Unit, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden (S.H., A.W.K., R.S., C.H., C.G., J.P., L.H.L., F.C.).

Rationale: Hyperglycemia -induced reactive oxygen species are key mediators of cardiac dysfunction. JunD (Jund proto-oncogene subunit), a member of the AP-1 (activator protein-1) family of transcription factors, is emerging as a major gatekeeper against oxidative stress. However, its contribution to redox state and inflammation in the diabetic heart remains to be elucidated.

Objective: The present study investigates the role of JunD in hyperglycemia-induced and reactive oxygen species-driven myocardial dysfunction.

Methods And Results: JunD mRNA and protein expression were reduced in the myocardium of mice with streptozotocin-induced diabetes mellitus as compared to controls. JunD downregulation was associated with oxidative stress and left ventricular dysfunction assessed by electron spin resonance spectroscopy as well as conventional and 2-dimensional speckle-tracking echocardiography. Furthermore, myocardial expression of free radical scavenger superoxide dismutase 1 and aldehyde dehydrogenase 2 was reduced, whereas the NOX2 (NADPH [nicotinamide adenine dinucleotide phosphatase] oxidase subunit 2) and NOX4 (NADPH [nicotinamide adenine dinucleotide phosphatase] oxidase subunit 4) were upregulated. The redox changes were associated with increased NF-κB (nuclear factor kappa B) binding activity and expression of inflammatory mediators. Interestingly, mice with cardiac-specific overexpression of JunD via the α MHC (α- myosin heavy chain) promoter (α MHC ) were protected against hyperglycemia-induced cardiac dysfunction. We also showed that JunD was epigenetically regulated by promoter hypermethylation, post-translational modification of histone marks, and translational repression by miRNA (microRNA)-673/menin. Reduced JunD mRNA and protein expression were confirmed in left ventricular specimens obtained from patients with type 2 diabetes mellitus as compared to nondiabetic subjects.

Conclusions: Here, we show that a complex epigenetic machinery involving DNA methylation, histone modifications, and microRNAs mediates hyperglycemia-induced JunD downregulation and myocardial dysfunction in experimental and human diabetes mellitus. Our results pave the way for tissue-specific therapeutic modulation of JunD to prevent diabetic cardiomyopathy.
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http://dx.doi.org/10.1161/CIRCRESAHA.120.317132DOI Listing
October 2020

Lower socioeconomic status predicts higher mortality and morbidity in patients with heart failure.

Heart 2021 Feb 7;107(3):229-236. Epub 2020 Aug 7.

Department of Medicine, Karolinska Institute, Stockholm, Sweden

Objective: It is not fully understood whether and how socioeconomic status (SES) has a prognostic impact in patients with heart failure (HF). We assessed SES and its association with patient characteristics and outcomes in a contemporary and well-characterised HF cohort.

Methods: Socioeconomic risk factors (SERF) were defined in the Swedish HF Registry based on income (low vs high according to the annual median value), education level (no degree/compulsory school vs university/secondary school) and living arrangement (living alone vs cohabitating).

Results: Of 44 631 patients, 21% had no, 33% one, 30% two and 16% three SERF. Patient characteristics strongly and independently associated with lower SES were female sex and no specialist referral. Additional independent associations were older age, more severe HF, heavier comorbidity burden, use of diuretics and less use of HF devices. Lower SES was associated with higher risk of HF hospitalisation/mortality, and overall cardiovascular and non-cardiovascular events. These associations persisted after extensive adjustment for patient characteristics, treatments and care. The magnitude of the association increased linearly with the increasing number of coexistent SERF: HR (95% CI) 1.09 (1.05 to 1.13) for one, 1.16 (1.12 to 1.20) for two and 1.22 (1.18 to 1.28) for three SERF (p<0.01).

Conclusions: In a contemporary and well-characterised HF cohort and after comprehensive adjustment for confounders, lower SES was linked with multiple factors such as less use of HF devices and age, but most strongly with female sex and lack of specialist referral; and associated with greater risk of morbidity/mortality.
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http://dx.doi.org/10.1136/heartjnl-2020-317216DOI Listing
February 2021

Acceleration of kidney function decline after incident hospitalization with cardiovascular disease: the Stockholm CREAtinine Measurements (SCREAM) project.

Eur J Heart Fail 2020 10 20;22(10):1790-1799. Epub 2020 Aug 20.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Aims: The cardiorenal syndrome refers to a bidirectional relationship between the kidney and the heart. However, epidemiological evidence of cardiovascular disease (CVD) as a risk factor for chronic kidney disease (CKD) progression is actually scarce.

Methods And Results: We examined the slopes of estimated glomerular filtration rate (eGFR) decline in the 2 years before vs. after an incident hospitalization with heart failure (HF) (n = 20 420), coronary heart disease (CHD) (n = 18 152), or stroke (n = 1808) using data from a complete laboratory data collection in Stockholm, Sweden between 2006 and 2011. eGFR slopes were estimated using mixed-effect models with unstructured residual correlation. Overall, incident hospitalization with HF and CHD, but not stroke, was significantly associated with a subsequent accelerated decline in eGFR, with a faster eGFR decline and greater slope change after HF than CHD. The pre-event vs. post-event eGFR slopes (mL/min/1.73 m per year) were -1.67 (-1.77 to -1.57) vs. -2.76 (-2.82 to -2.71), with a Δslope of -1.09 (-1.16 to -1.02) for HF; -1.09 (-1.20 to -0.98) vs. -1.87 (-1.92 to -1.81), with a Δslope of -0.78 (-0.85 to -0.70) for CHD; and -1.00 (-1.37 to -0.63) vs. -0.99 (-1.19 to -0.78), with a Δslope of 0.02 (-0.24 to 0.27) for stroke. The accelerated declines in eGFR after HF and CHD were consistent across the spectrum of eGFR, although pre-event eGFR slopes were steeper in lower eGFR (e.g. pre-event eGFR slope for HF -0.64 (-0.76 to -0.53) for eGFR ≥60 mL/min/1.73 m , -1.43 (-1.57 to -1.30) for eGFR 30-59 mL/min/1.73 m , and -2.42 (-2.71 to -2.12) for eGFR <30 mL/min/1.73 m ).

Conclusions: Incident hospitalization with cardiac diseases (i.e. HF and CHD) was significantly associated with a subsequent acceleration of eGFR decline.
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http://dx.doi.org/10.1002/ejhf.1968DOI Listing
October 2020

Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction: Treating Resistance, Impedance, and Compliance.

J Card Fail 2020 08 16;26(8):662-663. Epub 2020 Jul 16.

From the Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.

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http://dx.doi.org/10.1016/j.cardfail.2020.07.003DOI Listing
August 2020

Pragmatic approaches to the next generation of clinical trials in heart failure.

Authors:
Lars H Lund

Eur Heart J Cardiovasc Pharmacother 2020 09;6(5):282-283

Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

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http://dx.doi.org/10.1093/ehjcvp/pvaa085DOI Listing
September 2020

Heart Failure in Patients Undergoing Elective and Emergency Noncardiac Surgery: Still a Poorly Addressed Risk Factor.

J Card Fail 2020 Dec 9;26(12):1034-1042. Epub 2020 Jul 9.

Perioperative Medicine and Intensive Care, Karolinska University Hospital, Solna, Stockholm, Sweden; Section of Anaesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.

Background: Noncardiac surgery is increasingly offered to an older, more comorbid population. The aim was to characterize patients with the diagnosis of heart failure (HF) undergoing elective and emergency noncardiac surgery in a broad, contemporary Swedish cohort, and to assess the short- and long-term mortality in patients with HF as compared with patients without HF.

Methods And Results: Data from 200,638 and 97,129 patients undergoing elective and emergency surgical procedures at 23 Swedish university, county, and district hospitals during 2007 to 2013 were analyzed through linkage of the surgical Orbit Database to the National Patient and the Cause of Death registries. In total 7212 patients (3.6%) with a diagnosis of HF before surgery underwent elective and 6455 patients (6.6%) underwent emergency surgery. Patients with HF were older had more comorbidities, and higher mortality than patients without HF. Crude and adjusted risk ratios for 30-day mortality after elective surgery were 5.36 (95% confidence interval [CI] 4.67-6.16) and 1.79 (95% CI 1.50-2.14) (adjusted for comorbidities, surgical risk level, age, and sex). Corresponding data for emergency surgery was 3.84 (95% CI 3.58-4.12) and 1.48 (95% CI 1.31-1.62). Mortality in patients with HF after elective surgery at 30 days, 90 days, and 1 year was 3.2%, 6.5%, and 16.2% and after emergency surgery it was 13.7%, 22.4%, and 39.3%.

Conclusions: Patients with HF undergoing elective or emergency noncardiac surgery in a modern surgical setting have a substantial mortality risk and HF is both a risk factor and a strong marker for increasd risk. The reasons for the high mortality are not well-understood and warrant further attention.
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http://dx.doi.org/10.1016/j.cardfail.2020.06.015DOI Listing
December 2020

Is heart failure misdiagnosed in hospitalized patients with preserved ejection fraction? From the European Society of Cardiology - Heart Failure Association EURObservational Research Programme Heart Failure Long-Term Registry.

ESC Heart Fail 2020 10 2;7(5):2098-2112. Epub 2020 Jul 2.

Unit of Cardiology, Department of Medicine, Karolinska Institutet, and Heart and Vascular Theme, Karolinska University Hospital, Stockholm, Sweden.

Aims: In hospitalized patients with a clinical diagnosis of acute heart failure (HF) with preserved ejection fraction (HFpEF), the aims of this study were (i) to assess the proportion meeting the 2016 European Society of Cardiology (ESC) HFpEF criteria and (ii) to compare patients with restrictive/pseudonormal mitral inflow pattern (MIP) vs. patients with MIP other than restrictive/pseudonormal.

Methods And Results: We included hospitalized participants of the ESC-Heart Failure Association (HFA) EURObservational Research Programme (EORP) HF Long-Term Registry who had echocardiogram with ejection fraction (EF) ≥ 50% during index hospitalization. As no data on e', E/e' and left ventricular (LV) mass index were gathered in the registry, the 2016 ESC HFpEF definition was modified as follows: elevated B-type natriuretic peptide (BNP) (≥100 pg/mL for acute HF) and/or N-terminal pro-BNP (≥300 pg/mL) and at least one of the echocardiographic criteria: (i) presence of LV hypertrophy (yes/no), (ii) left atrial volume index (LAVI) of >34 mL/m ), or (iii) restrictive/pseudonormal MIP. Next, all patients were divided into four groups: (i) patients with restrictive/pseudonormal MIP on echocardiography [i.e. with presumably elevated left atrial (LA) pressure], (ii) patients with MIP other than restrictive/pseudonormal (i.e. with presumably normal LA pressure), (iii) atrial fibrillation (AF) group, and (iv) 'grey area' (no consistent description of MIP despite no report of AF). Of 6365 hospitalized patients, 1848 (29%) had EF ≥ 50%. Natriuretic peptides were assessed in 28%, LV hypertrophy in 92%, LAVI in 13%, and MIP in 67%. The 2016 ESC HFpEF criteria could be assessed in 27% of the 1848 patients and, if assessed, were met in 52%. Of the 1848 patients, 19% had restrictive/pseudonormal MIP, 43% had MIP other than restrictive/pseudonormal, 18% had AF and 20% were grey area. There were no differences in long-term all-cause or cardiovascular mortality, or all-cause hospitalizations or HF rehospitalizations between the four groups. Despite fewer non-cardiac comorbidities reported at baseline, patients with MIP other than restrictive/pseudonormal (i.e. with presumably normal LA pressure) had more non-cardiovascular (14.0 vs. 6.7 per 100 patient-years, P < 0.001) and cardiovascular non-HF (13.2 vs. 8.0 per 100 patient-years, P = 0.016) hospitalizations in long-term follow-up than patients with restrictive/pseudonormal MIP.

Conclusions: Acute HFpEF diagnosis could be assessed (based on the 2016 ESC criteria) in only a quarter of patients and confirmed in half of these. When assessed, only one in three patients had restrictive/pseudonormal MIP suggestive of elevated LA pressure. Patients with MIP other than restrictive/pseudonormal (suggestive of normal LA pressure) could have been misdiagnosed with acute HFpEF or had echocardiography performed after normalization of LA pressure. They were more often hospitalized for non-HF reasons during follow-up. Symptoms suggestive of acute HFpEF may in some patients represent non-HF comorbidities.
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http://dx.doi.org/10.1002/ehf2.12817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524216PMC
October 2020