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Wikström, Gerhard
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Publications (10 of 74) Show all publications
Lindmark, K., Boman, K., Olofsson, M., Tornblom, M., Levine, A., Castelo-Branco, A., . . . Wikström, G. (2019). Epidemiology of heart failure and trends in diagnostic work-up: a retrospective, population-based cohort study in Sweden. Clinical Epidemiology, 11, 231-244
Open this publication in new window or tab >>Epidemiology of heart failure and trends in diagnostic work-up: a retrospective, population-based cohort study in Sweden
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2019 (English)In: Clinical Epidemiology, ISSN 1179-1349, E-ISSN 1179-1349, Vol. 11, p. 231-244Article in journal (Refereed) Published
Abstract [en]

Purpose: The purpose of this study was to examine the trends in heart failure (HF) epidemiology and diagnostic work-up in Sweden.

Methods: Adults with incident HF (>= 2 ICD-10 diagnostic codes) were identified from linked national health registers (cohort 1, 2005-2013) and electronic medical records (cohort 2, 2010-2015; primary/secondary care patients from Uppsala and Vasterbotten). Trends in annual HF incidence rate and prevalence, risk of all-cause and cardiovascular disease (CVD)-related 1-year mortality and use of diagnostic tests 6 months before and after first HF diagnosis (cohort 2) were assessed.

Results: Baseline demographic and clinical characteristics were similar for cohort 1 (N=174,537) and 2 (N=8,702), with mean ages of 77.4 and 76.6 years, respectively; almost 30% of patients were aged >= 85 years. From 2010 to 2014, age-adjusted annual incidence rate of HF/1,000 inhabitants decreased (from 3.20 to 2.91, cohort 1; from 4.34 to 3.33, cohort 2), while age-adjusted prevalence increased (from 1.61% to 1.72% and from 2.15% to 2.18%, respectively). Age-adjusted 1-year all-cause and CVD-related mortality was higher in men than in women among patients in cohort 1 (all-cause mortality hazard ratio [HR] men vs women 1.07 [95% CI 1.06-1.09] and CVD-related mortality subdistribution HR for men vs women 1.04 [95% CI 1.02-1.07], respectively). While 83.5% of patients underwent N-terminal pro-B-type natriuretic peptide testing, only 36.4% of patients had an echocardiogram at the time of diagnosis, although this increased overtime. In the national prevalent HF population (patients with a diagnosis in 1997-2004 who survived into the analysis period; N=273,999), death from ischemic heart disease and myocardial infarction declined between 2005 and 2013, while death from HF and atrial fibrillation/flutter increased (P<0.0001 for trends over time).

Conclusion: The annual incidence rate of HF declined over time, while prevalence of HF has increased, suggesting that patients with HF were surviving longer over time. Our study confirms that previously reported epidemiological trends persist and remain to ensure proper diagnostic evaluation and management of patients with HF.

Keywords
diagnosis, heart failure, incidence rate, mortality, prevalence, real-world
National Category
Cardiac and Cardiovascular Systems Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-382363 (URN)10.2147/CLEP.S170873 (DOI)000464038900001 ()30962724 (PubMedID)
Available from: 2019-04-24 Created: 2019-04-24 Last updated: 2019-04-24Bibliographically approved
Pölzl, G., Allipour Birgani, S., Comin-Colet, J., Delgado, J. F., Fedele, F., Garcia-Gonzales, M. J., . . . Altenberger, J. (2019). Repetitive levosimendan infusions for patients with advanced chronic heart failure in the vulnerable post-discharge period. ESC Heart Failure, 6(1), 174-181
Open this publication in new window or tab >>Repetitive levosimendan infusions for patients with advanced chronic heart failure in the vulnerable post-discharge period
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2019 (English)In: ESC Heart Failure, E-ISSN 2055-5822, Vol. 6, no 1, p. 174-181Article in journal (Refereed) Published
Abstract [en]

Hospitalization for acute heart failure (HF) is associated with a substantial morbidity burden and with associated healthcare costs and an increased mortality risk. However, few if any major medical innovations have been witnessed in this area in recent times. Levosimendan is a first-in-class calcium sensitizer and potassium channel opener indicated for the management of acute HF. Experience in several clinical studies has indicated that administration of intravenous levosimendan in intermittent cycles may reduce hospitalization and mortality rates in patients with advanced HF; however, none of those trials were designed or powered to give conclusive insights into that possibility. This paper describes the rationale and protocol of LeoDOR (levosimendan infusions for patients with advanced chronic heart failure), a randomized, double-blind, placebo-controlled, international, multicentre trial that will explore the efficacy and safety of intermittent levosimendan therapy, in addition to optimized standard therapy, in patients following hospitalization for acute HF. Salient features of LeoDOR include the use of two treatment regimens, in order to evaluate the effects of different schedules and doses of levosimendan during a 12 week treatment phase, and the use of a global rank primary endpoint, in which all patients are ranked across three hierarchical groups ranging from time to death or urgent heart transplantation or implantation of a ventricular assist device to time to rehospitalization and, lastly, time-averaged proportional change in N-terminal pro-brain natriuretic peptide. Secondary endpoints include changes in HF symptoms and functional status at 14 weeks.

Place, publisher, year, edition, pages
WILEY PERIODICALS, INC, 2019
Keywords
Levosimendan, Advanced heart failure, Randomized controlled trial, Hospitalization, N-terminal pro-brain natriuretic peptide, Global rank endpoint
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-379275 (URN)10.1002/ehf2.12366 (DOI)000459632300021 ()30378288 (PubMedID)
Available from: 2019-03-18 Created: 2019-03-18 Last updated: 2019-03-18Bibliographically approved
Kylhammar, D., Kjellström, B., Hjalmarsson, C., Jansson, K., Nisell, M., Söderberg, S., . . . Rådegran, G. (2018). A comprehensive risk stratification at early follow-up determines prognosis in pulmonary arterial hypertension. European Heart Journal, 39(47), 4175-4181
Open this publication in new window or tab >>A comprehensive risk stratification at early follow-up determines prognosis in pulmonary arterial hypertension
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2018 (English)In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, no 47, p. 4175-4181Article in journal (Refereed) Published
Abstract [en]

Aims: Guidelines recommend a goal-oriented treatment approach in pulmonary arterial hypertension (PAH). The aim is to reach a low-risk profile, as determined by a risk assessment instrument. This strategy is incompletely validated. We aimed to investigate the bearing of such risk assessment and the benefit of reaching a low-risk profile.

Methods and results: Five hundred and thirty PAH patients were included. Follow-up assessments performed after a median of 4 (interquartile range 3–5) months were available for 383 subjects. Patients were classified as ‘Low’, ‘Intermediate’, or ‘High risk’ and the benefit of reaching the ‘Low risk’ group was estimated. Survival differed (P < 0.001) between the risk groups at baseline and at follow-up. Survival was similar for patients who remained in or improved to the ‘Low risk’ group. Survival was similar for patients who remained in or worsened to the ‘Intermediate risk’ or ‘High risk’ groups. Irrespective of follow-up risk group, survival was better (P < 0.001) for patients with a higher proportion of variables at low risk. Results were unchanged after excluding patients with idiopathic PAH >65 years at diagnosis, and when patients with idiopathic or connective tissue disease-associated PAH were analysed separately. Patients in the ‘Low risk’ group at follow-up exhibited a reduced mortality risk (hazard ratio 0.2, 95% confidence interval 0.1–0.4 in multivariable analysis adjusted for age, sex and PAH subset), as compared to patients in the ‘Intermediate risk’ or ‘High risk’ groups.

Conclusion: These findings suggest that comprehensive risk assessments and the aim of reaching a low-risk profile are valid in PAH.

Keywords
Prognosis, Survival, Goal-oriented treatment, Guidelines, PAH
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-377378 (URN)10.1093/eurheartj/ehx257 (DOI)000456854500010 ()28575277 (PubMedID)
Funder
Eli Lilly and CompanyGlaxoSmithKline (GSK)Swedish Association of Local Authorities and Regions
Available from: 2019-02-25 Created: 2019-02-25 Last updated: 2019-02-25Bibliographically approved
Lundgren, J., Sandqvist, A., Hedeland, M., Bondesson, U., Wikström, G. & Rådegran, G. (2018). Alterations in plasma L-arginine and methylarginines in heart failure and after heart transplantation. Scandinavian Cardiovascular Journal, 52(4), 196-204
Open this publication in new window or tab >>Alterations in plasma L-arginine and methylarginines in heart failure and after heart transplantation
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2018 (English)In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 52, no 4, p. 196-204Article in journal (Refereed) Published
Abstract [en]

Objective: Endothelial function, including the nitric oxide (NO)-pathway, has previously been extensively investigated in heart failure (HF). In contrast, studies are lacking on the NO pathway after heart transplantation (HT). We therefore investigated substances in the NO pathway prior to and after HT in relation to hemodynamic parameters.

Design: 12 patients (median age 50.0 yrs, 2 females), heart transplanted between June 2012 and February 2014, evaluated at our hemodynamic lab, at rest, prior to HT, as well as four weeks and six months after HT were included. All patients had normal left ventricular function post-operatively and none had post-operative pulmonary hypertension or acute cellular rejection requiring therapy at the evaluations. Plasma concentrations of ADMA, SDMA, L-Arginine, L-Ornithine and L-Citrulline were analyzed at each evaluation.

Results: In comparison to controls, the plasma L-Arginine concentration was low and ADMA high in HF patients, resulting in low L-Arginine/ADMA-ratio pre-HT. Already four weeks after HT L-Arginine was normalized whereas ADMA remained high. Consequently the L-Arginine/ADMA-ratio improved, but did not normalize. The biomarkers remained unchanged at the six-month evaluation and the L-Arginine/ADMA-ratio correlated inversely to pulmonary vascular resistance (PVR) six months post-HT.

Conclusions: Plasma L-Arginine concentrations normalize after HT. However, as ADMA is unchanged, the L-Arginine/ADMA-ratio remained low and correlated inversely to PVR. Together these findings suggest that (i) the L-Arginine/ADMA-ratio may be an indicator of pulmonary vascular tone after HT, and that (ii) NO-dependent endothelial function is partly restored after HT. Considering the good postoperative outcome, the biomarker levels may be considered “normal” after HT.

Keywords
Nitric Oxide, ADMA, L-Arginine, heart transplantation, heart failure, right heart catheterization
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-358210 (URN)10.1080/14017431.2018.1459823 (DOI)000436583700005 ()29648475 (PubMedID)
Available from: 2018-08-31 Created: 2018-08-31 Last updated: 2018-09-20Bibliographically approved
Akhter, T., Wikström, G., Larsson, M., Bondesson, U., Hedeland, M. & Naessén, T. (2018). Dimethylarginines correlate to common carotid artery wall layer dimensions and cardiovascular risk factors in pregnant women with and without preeclampsia. Paper presented at 86th Congress of the European-Atherosclerosis-Society (EAS), MAY 05-08, 2018, Lisbon, PORTUGAL. Atherosclerosis, 275, E69-E70
Open this publication in new window or tab >>Dimethylarginines correlate to common carotid artery wall layer dimensions and cardiovascular risk factors in pregnant women with and without preeclampsia
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2018 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 275, p. E69-E70Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
ELSEVIER IRELAND LTD, 2018
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-367146 (URN)10.1016/j.atherosclerosis.2018.06.192 (DOI)000442512600206 ()
Conference
86th Congress of the European-Atherosclerosis-Society (EAS), MAY 05-08, 2018, Lisbon, PORTUGAL
Available from: 2018-11-28 Created: 2018-11-28 Last updated: 2018-11-28Bibliographically approved
Henrohn, D., Björkstrand, K., Lundberg, J. O., Granstam, S.-O., Baron, T., Ingimarsdóttir, I. J., . . . Wikström, G. (2018). Effects of Oral Supplementation With Nitrate-Rich Beetroot Juice in Patients With Pulmonary Arterial Hypertension-Results From BEET-PAH, an Exploratory Randomized, Double-Blind, Placebo-Controlled, Crossover Study.. Journal of Cardiac Failure, 24(10), 640-653
Open this publication in new window or tab >>Effects of Oral Supplementation With Nitrate-Rich Beetroot Juice in Patients With Pulmonary Arterial Hypertension-Results From BEET-PAH, an Exploratory Randomized, Double-Blind, Placebo-Controlled, Crossover Study.
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2018 (English)In: Journal of Cardiac Failure, ISSN 1071-9164, E-ISSN 1532-8414, Vol. 24, no 10, p. 640-653Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The nitrate-nitrite-nitric oxide (NO) pathway may represent a potential therapeutic target in patients with pulmonary arterial hypertension (PAH). We explored the effects of dietary nitrate supplementation, with the use of nitrate-rich beetroot juice (BRJ), in patients with PAH.

METHODS AND RESULTS: We prospectively studied 15 patients with PAH in an exploratory randomized, double-blind, placebo-controlled, crossover trial. The patients received nitrate-rich beetroot juice (∼16 mmol nitrate per day) and placebo in 2 treatment periods of 7 days each. The assessments included; exhaled NO and NO flow-independent parameters (alveolar NO and bronchial NO flux), plasma and salivary nitrate and nitrite, biomarkers and metabolites of the NO-system, N-terminal pro-B-type natriuretic peptide, echocardiography, ergospirometry, diffusing capacity of the lung for carbon monoxide, and the 6-minute walk test. Compared with placebo ingestion of BRJ resulted in increases in; fractional exhaled NO at all flow-rates, alveolar NO concentrations and bronchial NO flux, and plasma and salivary levels of nitrate and nitrite. Plasma ornithine levels decreased and indices of relative arginine availability increased after BRJ compared to placebo. A decrease in breathing frequency was observed during ergospirometry after BRJ. A tendency for an improvement in right ventricular function was observed after ingestion of BRJ. In addition a tendency for an increase in the peak power output to peak oxygen consumption ratio (W peak/VO2 peak) was observed, which became significant in patients reaching an increase of plasma nitrite >30% (responders).

CONCLUSIONS: BRJ administered for 1 week increases pulmonary NO production and the relative arginine bioavailability in patients with PAH, compared with placebo. An increase in the W peak/VO2 peak ratio was observed after BRJ ingestion in plasma nitrite responders. These findings indicate that supplementation with inorganic nitrate increase NO synthase-independent NO production from the nitrate-nitrite-NO pathway.

Keywords
Pulmonary arterial hypertension, beetroot juice, nitrate, nitric oxide, nitrite
National Category
Basic Medicine
Identifiers
urn:nbn:se:uu:diva-366975 (URN)10.1016/j.cardfail.2018.09.010 (DOI)000452812400004 ()30244181 (PubMedID)
Available from: 2018-11-27 Created: 2018-11-27 Last updated: 2019-04-17Bibliographically approved
Lindmark, K., Boman, K., Olofsson, M., Wirta, S. B., Proenca, C. C., Levine, A., . . . Wikström, G. (2018). Increased all-cause mortality in newly diagnosed patients with heart failure between 2006 and 2012: a retrospective, population-based study in Sweden. European Journal of Heart Failure, 20(S1), 6-6
Open this publication in new window or tab >>Increased all-cause mortality in newly diagnosed patients with heart failure between 2006 and 2012: a retrospective, population-based study in Sweden
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2018 (English)In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 20, no S1, p. 6-6Article in journal, Meeting abstract (Other academic) Published
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-365131 (URN)000434123900004 ()
Available from: 2018-11-09 Created: 2018-11-09 Last updated: 2018-11-09Bibliographically approved
Sandqvist, A., Schneede, J., Kylhammar, D., Henrohn, D., Lundgren, J., Hedeland, M., . . . Wikström, G. (2018). Plasma l-arginine levels distinguish pulmonary arterial hypertension from left ventricular systolic dysfunction. Heart and Vessels, 33(3), 255-263
Open this publication in new window or tab >>Plasma l-arginine levels distinguish pulmonary arterial hypertension from left ventricular systolic dysfunction
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2018 (English)In: Heart and Vessels, ISSN 0910-8327, E-ISSN 1615-2573, Vol. 33, no 3, p. 255-263Article in journal (Refereed) Published
Abstract [en]

Pulmonary arterial hypertension (PAH) is a life-threatening condition, characterized by an imbalance of vasoactive substances and remodeling of pulmonary vasculature. Nitric oxide, formed from l-arginine, is essential for homeostasis and smooth muscle cell relaxation in PAH. Our aim was to compare plasma concentrations of l-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) in PAH compared to left ventricular systolic dysfunction (LVSD) and healthy subjects. This was an observational, multicenter study comparing 21 patients with PAH to 14 patients with LVSD and 27 healthy subjects. Physical examinations were obtained and blood samples were collected. Plasma levels of ADMA, SDMA, l-arginine, l-ornithine, and l-citrulline were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma levels of ADMA and SDMA were higher, whereas l-arginine and l-arginine/ADMA ratio were lower in PAH patients compared to healthy subjects (p < 0.001). Patients with PAH also had lower levels of l-arginine than patients with LVSD (p < 0.05). l-Arginine correlated to 6 min walking distance (6MWD) (r (s) = 0.58, p = 0.006) and l-arginine/ADMA correlated to WHO functional class (r (s) = -0.46, p = 0.043) in PAH. In conclusion, l-arginine levels were significantly lower in treatment na < ve PAH patients compared to patients with LVSD. Furthermore, l-arginine correlated with 6MWD in PAH. l-arginine may provide useful information in differentiating PAH from LVSD.

Place, publisher, year, edition, pages
SPRINGER, 2018
Keywords
Pulmonary arterial hypertension, Left heart failure, Systolic dysfunction, L-Arginine, Dimethylarginines
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-350494 (URN)10.1007/s00380-017-1055-7 (DOI)000426278900005 ()28975394 (PubMedID)
Available from: 2018-05-09 Created: 2018-05-09 Last updated: 2018-05-09Bibliographically approved
Arvidsson, S., Henein, M. Y., Wikström, G., Suhr, O. B. & Lindqvist, P. (2018). Right ventricular involvement in transthyretin amyloidosis. Amyloid: Journal of Protein Folding Disorders, 25(3), 160-166
Open this publication in new window or tab >>Right ventricular involvement in transthyretin amyloidosis
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2018 (English)In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 25, no 3, p. 160-166Article in journal (Refereed) Published
Abstract [en]

Background: The extent of right ventricular (RV) involvement in transthyretin amyloidosis (ATTR) is unknown.Objectives: This study sought to establish the degree of RV involvement in ATTR amyloidosis, and compare findings with RV involvement in hypertrophic cardiomyopathy (HCM).Methods: Forty-two patients with ATTR amyloidosis and echocardiographic evidence of cardiac amyloidosis (cardiac ATTR), 19 ATTR patients with normal left ventricular (LV) wall thickness (non-cardiac ATTR), 25 patients with diagnosed HCM and 30 healthy controls were included in this study. Echocardiographic measurements for conventional parameters, as well as RV global and segmental strain, were recorded.Results: When comparing RV structure and function between cardiac ATTR amyloidosis and HCM patients, only segmental strain differed between the two groups. In cardiac ATTR amyloidosis, we found an RV apex-to-base strain gradient with highest deformation in the apex. This pattern was reversed in patients with HCM.Conclusions: RV involvement is common in cardiac ATTR patients. The present study also detected an RV apical sparing pattern in patients with ATTR cardiomyopathy, similar to what has previously been described for the left ventricle in these patients. This pattern was not seen in HCM patients. Further studies are needed to assess the clinical importance of these findings.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2018
Keywords
Hypertrophic cardiomyopathy, apical sparing, strain, amyloid cardiomyopathy, right ventricle
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-372684 (URN)10.1080/13506129.2018.1493989 (DOI)000451980700004 ()30193533 (PubMedID)
Funder
Swedish Heart Lung FoundationVästerbotten County Council, VLL 365301
Available from: 2019-01-08 Created: 2019-01-08 Last updated: 2019-01-08Bibliographically approved
Fu, M., Ahrenmark, U., Berglund, S., Lindholm, C. J., Lehto, A., Broberg, A. M., . . . Andersson, B. (2017). Adherence to optimal heart rate control in heart failure with reduced ejection fraction: insight from a survey of heart rate in heart failure in Sweden (HR-HF study). Clinical Research in Cardiology, 106(12), 960-973
Open this publication in new window or tab >>Adherence to optimal heart rate control in heart failure with reduced ejection fraction: insight from a survey of heart rate in heart failure in Sweden (HR-HF study)
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2017 (English)In: Clinical Research in Cardiology, ISSN 1861-0684, E-ISSN 1861-0692, Vol. 106, no 12, p. 960-973Article in journal (Refereed) Published
Abstract [en]

Despite that heart rate (HR) control is one of the guideline-recommended treatment goals for heart failure (HF) patients, implementation has been painstakingly slow. Therefore, it would be important to identify patients who have not yet achieved their target heart rates and assess possible underlying reasons as to why the target rates are not met. The survey of HR in patients with HF in Sweden (HR-HF survey) is an investigator-initiated, prospective, multicenter, observational longitudinal study designed to investigate the state of the art in the control of HR in HF and to explore potential underlying mechanisms for suboptimal HR control with focus on awareness of and adherence to guidelines for HR control among physicians who focus on the contributing role of beta-blockers (BBs). In 734 HF patients the mean HR was 68 +/- 12 beats per minute (bpm) (37.2% of the patients had a HR > 70 bpm). Patients with HF with reduced ejection fraction (HFrEF) (n = 425) had the highest HR (70 +/- 13 bpm, with 42% > 70 bpm), followed by HF with preserved ejection fraction and HF with mid-range ejection fraction. Atrial fibrillation, irrespective of HF type, had higher HR than sinus rhythm. A similar pattern was observed with BB treatment. Moreover, non-achievement of the recommended target HR (< 70 bpm) in HFrEF and sinus rhythm was unrelated to age, sex, cardiovascular risk factors, cardiovascular diseases, and comorbidities, but was related to EF and the clinical decision of the physician. Approximately 50% of the physicians considered a HR of > 70 bpm optimal and an equal number considered a HR of > 70 bpm too high, but without recommending further action. Furthermore, suboptimal HR control cannot be attributed to the use of BBs because there was neither a difference in use of BBs nor an interaction with BBs for HR > 70 bpm compared with HR < 70 bpm. Suboptimal control of HR was noted in HFrEF with sinus rhythm, which appeared to be attributable to physician decision making rather than to the use of BBs. Therefore, our results underline the need for greater attention to HR control in patients with HFrEF and sinus rhythm and thus a potential for improved HF care.

Place, publisher, year, edition, pages
SPRINGER HEIDELBERG, 2017
Keywords
Heart rate, Heart failure, Awareness, Adherence, Beta-blocker
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-342660 (URN)10.1007/s00392-017-1146-6 (DOI)000416042400004 ()28795299 (PubMedID)
Available from: 2018-02-27 Created: 2018-02-27 Last updated: 2018-02-27Bibliographically approved
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