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  • 1.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Benson, Lina
    Karolinska Institute, Sweden.
    Edner, Magnus
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lund, Lars H.
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Association Between Use of Statins and Mortality in Patients With Heart Failure and Ejection Fraction of greater than= 50%2015In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 8, no 5, p. 862-870Article in journal (Refereed)
    Abstract [en]

    Background The pathophysiology of heart failure with preserved ejection fraction is poorly understood, but may involve a systemic proinflammatory state. Therefore, statins might improve outcomes in patients with heart failure with preserved ejection fraction defined as 50%. Methods and Results Of 46 959 unique patients in the prospective Swedish Heart Failure Registry, 9140 patients had heart failure and ejection fraction 50% (age 7711 years, 54.0% women), and of these, 3427 (37.5%) were treated with statins. Propensity scores for statin treatment were derived from 40 baseline variables. The association between statin use and primary (all-cause mortality) and secondary (separately, cardiovascular mortality, and combined all-cause mortality or cardiovascular hospitalization) end points was assessed with Cox regressions in a population matched 1:1 based on age and propensity score. In the matched population, 1-year survival was 85.1% for statin-treated versus 80.9% for untreated patients (hazard ratio, 0.80; 95% confidence interval, 0.72-0.89; Pless than0.001). Statins were also associated with reduced cardiovascular death (hazard ratio, 0.86; 95% confidence interval, 0.75-0.98; P=0.026) and composite all-cause mortality or cardiovascular hospitalization (hazard ratio, 0.89; 95% confidence interval, 0.82-0.96; P=0.003). Conclusions In heart failure with ejection fraction 50%, the use of statins was associated with improved outcomes. The mechanisms should be evaluated and the effects tested in a randomized trial.

  • 2.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Benson, Lina
    Karolinska Institute, Sweden.
    Edner, Magnus
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lund, Lars H.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Association Between Use of Statins and Outcomes in Heart Failure With Reduced Ejection Fraction Prospective Propensity Score Matched Cohort Study of 21 864 Patients in the Swedish Heart Failure Registry2015In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 8, no 2, p. 252-260Article in journal (Refereed)
    Abstract [en]

    Background-In heart failure (HF) with reduced ejection fraction, randomized trials of statins did not demonstrate improved outcomes. However, randomized trials may not always be generalizable. The aim was to determine whether statins are associated with improved outcomes in an unselected nationwide population of patients with HF with reduced ejection fraction overall and in relation to ischemic heart disease (IHD). Methods and Results-In the Swedish Heart Failure Registry, 21 864 patients with HF with reduced ejection fraction (age +/- SD, 72+/-12 years; 29% women), of whom 10 345 (47%) were treated with statins, were studied. Propensity scores for statin use were derived from 42 baseline variables. The associations between statin use and outcomes were assessed with Cox regressions in a population matched 1: 1 based on propensity score and age and in the overall population with adjustment for propensity score and age. The primary outcome was all-cause mortality; secondary outcomes were cardiovascular mortality; HF hospitalization; and combined all-cause mortality or cardiovascular hospitalization. Survival at 1 year in the matched population was 83% for statin-treated versus 79% for untreated patients (hazard ratio, 0.81; 95% confidence interval, 0.76-0.86; Pless than0.001). In the unmatched population, 1-year survival was 85% for statin-treated versus 79% for untreated patients, hazard ratio after adjustment for propensity score and age was 0.84 (95% confidence interval, 0.80-0.89; Pless than0.001). No examined baseline variables interacted with statin use except for IHD (P=0.001), with a hazard ratio of 0.76 (95% confidence interval, 0.70-0.82, Pless than0.001) with IHD and 0.95 (95% confidence interval, 0.85-1.07; P=0.430 without IHD. Statin use was also associated with reduced risk for all 3 secondary outcomes. Conclusions-In an unselected nationwide population of patients with HF with reduced ejection fraction, statins were associated with improved outcomes, specifically in the presence of IHD. This contrasts with previous randomized controlled trials. Additional randomized controlled trials with more generalized inclusion or focused on IHD may be warranted.

  • 3.
    Das, Debraj
    et al.
    University of Alberta, Canada.
    Savarese, Gianluigi
    Karolinska Institute, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Fu, Michael
    Department Med, Sweden.
    Howlett, Jonathan
    University of Calgary, Canada.
    Ezekowitz, Justin A.
    University of Alberta, Canada.
    Lund, Lars H.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Ivabradine in Heart Failure The Representativeness of SHIFT (Systolic Heart Failure Treatment With the IF Inhibitor Ivabradine Trial) in a Broad Population of Patients With Chronic Heart Failure2017In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 10, no 9, article id e004112Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The sinus node inhibitor ivabradine was approved for patients with heart failure (HF) after the ivabradine and outcomes in chronic HF (SHIFT [Systolic Heart Failure Treatment With the IF Inhibitor Ivabradine Trial]) trial. Our objective was to characterize the proportion of patients with HF eligible for ivabradine and the representativeness of the SHIFT trial enrollees compared with those in the Swedish Heart Failure Registry. METHODS AND RESULTS: We examined 26 404 patients with clinical HF from the Swedish Heart Failure Registry and divided them into SHIFT type (left ventricular ejection fraction amp;lt; 40%, New York Heart Association class II-IV, sinus rhythm, and heart rate amp;gt;= 70 beats per minute) and nonSHIFT type. Baseline characteristics and medication use were compared and change in eligibility over time was reported at 6 months and 1 year in a subset of patients. Overall, 14.2% (n= 3741) of patients were SHIFT type. These patients were more likely to be younger, men, have diabetes mellitus, ischemic heart disease, lower left ventricular ejection fraction, and more recent onset HF (amp;lt; 6 months; all, Pamp;lt; 0.001). Although 88.9% of SHIFT type and 88.5% of non-SHIFT type (P= 0.421) were receiving selected beta-blockers, only 58.8% and 67.3% (Pamp;lt; 0.001) were on amp;gt; 50% of target dose. From those patients who had repeated visits within 6 months (n= 5420) and 1 year (n= 6840), respectively, 10.2% (n= 555) and 10.6% (n= 724) of SHIFT-type patients became ineligible, 77.3% (n= 4188) and 77.3% (n= 5287) remained ineligible, and 4.6% (n= 252) and 4.9% (n= 335) of non-SHIFT-type patients became eligible for initiation of ivabradine. CONCLUSIONS: From the Swedish Heart Failure Registry, 14.2% of patients with HF were eligible for ivabradine. These patients more commonly were not receiving target beta-blocker dose. Over time, a minority of patients became ineligible and an even smaller minority became eligible.

  • 4.
    Li, Shi-Jun
    et al.
    Ostra Hospital, Sweden; Chinese Peoples Liberat Army Gen Hospital, Peoples R China.
    Sartipy, Ulrik
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Lund, Lars H.
    Karolinska Institute, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Adiels, Martin
    University of Gothenburg, Sweden.
    Petzold, Max
    University of Gothenburg, Sweden.
    Fu, Michael
    Ostra Hospital, Sweden.
    Prognostic Significance of Resting Heart Rate and Use of beta-Blockers in Atrial Fibrillation and Sinus Rhythm in Patients With Heart Failure and Reduced Ejection Fraction Findings From the Swedish Heart Failure Registry2015In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 8, no 5, p. 871-879Article in journal (Refereed)
    Abstract [en]

    Background In heart failure and reduced ejection fraction, the prognostic role of heart rate (HR) in atrial fibrillation (AF) is unknown and the effectiveness of -blockers has recently been questioned in AF. Methods and Results A total of 18 858 patients with heart failure and reduced ejection fraction registered with Swedish Heart Failure Registry were included in this study: patients with sinus rhythm (SR; n=11 466) and patients with AF (n=7392). The outcome measure was all-cause mortality. Compared with HR 60 beats per minute, the adjusted hazard ratios for mortality in SR were 1.26 for HR=61 to 70 beats per minute, 1.37 for HR=71 to 80 beats per minute, 1.52 for HR=81 to 90 beats per minute, 1.63 for HR=91 to 100 beats per minute, and 2.69 for HR greater than100 beats per minute. However, in AF, the hazard ratio increased only for HR greater than100 beats per minute (1.30; P=0.001). -blocker use was associated with reduced mortality in SR (hazard ratio, 0.77; P=0.011) and in AF (hazard ratio, 071; Pless than0.001). For -blocker use in SR, the hazard ratio gradually increased with HR increment, whereas in AF, the hazard ratio significantly increased only for HR greater than100 beats per minute (1.29; P=0.003) compared with HR 60 beats per minute. Conclusions In patients with heart failure and reduced ejection fraction, a higher HR was associated with increased mortality in SR, but in AF, this is true only for HR greater than100 beats per minute. -blocker use was associated with reduced mortality both in SR and in AF.

  • 5.
    Lim, Shir Lynn
    et al.
    Department of Cardiology, National University Heart Center, Singapore.
    Benson, Lina
    Department of Clinical Science and Education, Södersjukhuset, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lam, Carolyn S. P.
    Department of Cardiology, National Heart Center, Singapore; Duke-NUS Graduate Medical School, Singapore.
    Lund, Lars H.
    Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
    Association Between Use of Long-Acting Nitrates and Outcomes in Heart Failure With Preserved Ejection Fraction2017In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 10, no 4, article id e003534Article in journal (Refereed)
    Abstract [en]

    Nitrates may be beneficial in heart failure with preserved ejection fraction (HFpEF) by enhancing cGMP signaling and improving hemodynamics, but real-world data on potential efficacy are lacking.

  • 6.
    Lund, Lars H
    et al.
    Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Svennblad, Bodil
    Uppsala Clinical Research Center, Sweden.
    Melhus, Håkan
    Uppsala University, Sweden.
    Hallberg, Pär
    Uppsala University, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Edner, Magnus
    Karolinska Institutet, Stockholm, Sweden.
    Association of spironolactone use with all-cause mortality in heart failure: a propensity scored cohort study2013In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 6, no 2, p. 174-183Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In 3 randomized controlled trials in heart failure (HF), mineralocorticoid receptor antagonists reduced mortality. The net benefit from randomized controlled trials may not be generalizable, and eplerenone was, but spironolactone was not, studied in mild HF. We tested the hypothesis that spironolactone is associated with reduced mortality also in a broad unselected contemporary population with HF and reduced ejection fraction, in particular New York Heart Association (NYHA) I-II.

    METHODS AND RESULTS: We prospectively studied 18 852 patients (age 71±12 years; 28% women) with NYHA I-IV and ejection fraction <40% who were registered in the Swedish Heart Failure Registry between 2000 and 2012 and who were (n=6551) or were not (n=12 301) treated with spironolactone. We derived propensity scores for spironolactone treatment based on 41 covariates. We assessed survival by Cox regression with adjustment for propensity scores and with matching based on propensity score. We performed sensitivity and residual confounding analyses and analyzed the NYHA I-II and III-IV subgroups separately. One-year survival was 83% versus 84% in treated versus untreated patients (log rank P<0.001). After adjustment for propensity scores, the hazard ratio for spironolactone was 1.05 (95% confidence interval, 1.00-1.11; P=0.054). Spironolactone interacted with NYHA (P<0.001). In the NYHA I-II subgroup, after adjustment for propensity scores, the hazard ratio for spironolactone was 1.11 (95% confidence interval, 1.02-1.21; P=0.019).

    CONCLUSIONS: In an unselected contemporary population of HF with reduced ejection fraction, spironolactone was not associated with reduced mortality. The net benefits of spironolactone may be lower outside the clinical trial setting and in milder HF.

  • 7.
    Savarese, Gianluigi
    et al.
    Karolinska Institute, Sweden.
    Hage, Camilla
    Karolinska Institute, Sweden.
    Orsini, Nicola
    Karolinska Institute, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Perrone-Filardi, Pasquale
    University of Naples Federico II, Italy.
    Rosano, Giuseppe M. C.
    St Georges University, England; IRCCS San Raffaele Pisana, Italy.
    Lund, Lars H.
    Karolinska Institute, Sweden.
    Reductions in N-Terminal Pro-Brain Natriuretic Peptide Levels Are Associated With Lower Mortality and Heart Failure Hospitalization Rates in Patients With Heart Failure With Mid-Range and Preserved Ejection Fraction2016In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 9, no 11, article id e003105Article in journal (Refereed)
    Abstract [en]

    Background-In heart failure with mid-range ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF), feasible surrogate end points are needed for phase II trials. The aim was to assess whether a reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with improved mortality/morbidity in an unselected population of HFmrEF and HFpEF patients. Methods and Results-In the Swedish Heart Failure Registry, HFmrEF (EF=40%-49%) and HFpEF (EF=50%) patients reporting at least 2 consecutive outpatient NT-proBNP assessments were prospectively studied. Associations between reduction in NT-proBNP and overall mortality, HF hospitalization, and their composite were assessed by multivariable Cox regressions, with NT-proBNP changes modeled as binary (decrease/increase) or quantitative predictor by restricted cubic splines. In 650 patients, at a median of 7 months between the 2 measurements of NT-proBNP and over a median followup of 1.65 years, 361 patients (55%) showed a reduction and 289 patients (45%) an increase in NT-proBNP. Change in NT-proBNP was associated with risk of outcomes. Fifty-seven patients (16%) who decreased their NT-proBNP versus 78 patients (27%) who increased it died from any cause (adjusted hazard ratio=0.53; 95% confidence interval=0.36-0.77), 61 (17%) versus 86 (30%) were hospitalized for HF (hazard ratio=0.41; 95% confidence interval=0.29-0.60), and 96 (27%) versus 125 (43%) reported the composite outcome (hazard ratio=0.46; 95% confidence interval=0.34-0.62). These findings were replicated in HFmrEF and HFpEF separately. Conclusions-In HFmrEF and HFpEF during routine care, decreases in NT-proBNP were associated with improved mortality and morbidity. Studies to determine whether NT-proBNP changes in response to therapy predict drug efficacy are needed.

  • 8.
    Tromp, Jasper
    et al.
    University of Groningen, Netherlands .
    van der Pol, Atze
    University of Groningen, Netherlands .
    Klip, IJsbrand T.
    University of Groningen, Netherlands .
    de Boer, Rudolf A.
    University of Groningen, Netherlands .
    Jaarsma, Tiny
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Arts and Sciences.
    van Gilst, Wiek H.
    University of Groningen, Netherlands .
    Voors, Adriaan A.
    University of Groningen, Netherlands .
    van Veldhuisen, Dirk J.
    University of Groningen, Netherlands .
    van der Meer, Peter
    University of Groningen, Netherlands .
    Fibrosis Marker Syndecan-1 and Outcome in Patients With Heart Failure With Reduced and Preserved Ejection Fraction2014In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 7, no 3, p. 457-U119Article in journal (Refereed)
    Abstract [en]

    Background-Syndecan-1 is a member of the proteoglycan family involved in cell-matrix interactions. Experimental studies showed that syndecan-1 is associated with inflammation in acute myocardial infarction and remodeling. The goal of this study was to explore the role of syndecan-1 in human heart failure (HF). Methods and Results-We analyzed plasma syndecan-1 levels in 567 patients with chronic HF. Primary end point was a composite of all-cause mortality and rehospitalization for HF at 18 months. Mean age was 71.0 +/- 11.0 years, 38% was women, and mean left ventricular ejection fraction was 32.5 +/- 14.0%. Median syndecan-1 levels were 20.1 ng/mL (interquartile range, 13.9-27.7 ng/mL). Patients with higher syndecan-1 levels were more often men, had higher N-terminal probrain-type natriuretic peptide levels, and worse renal function. Multivariable regression analyses showed a positive correlation between syndecan-1 levels and markers of fibrosis and remodeling but no correlation with inflammation markers. Interaction analysis revealed an interaction between left ventricular ejection fraction and syndecan-1 (P=0.047). A doubling of syndecan-1 was associated with an increased risk of the primary outcome in patients with HF with preserved ejection fraction (hazard ratio, 2.10; 95% confidence interval, 1.14-3.86; P=0.017) but not in patients with HF with reduced ejection fraction (hazard ratio, 0.95; 95% confidence interval, 0.71-1.27; P=0.729). Finally, syndecan-1 enhanced risk classification in patients with HF with preserved ejection fraction when added to a prediction model with established risk factors. Conclusions-In patients with HF, syndecan-1 levels correlate with fibrosis biomarkers pointing toward a role in cardiac remodeling. Syndecan-1 was associated with clinical outcome in patients with HF with preserved ejection fraction but not in patients with HF with reduced ejection fraction.

  • 9.
    van Deursen, Vincent M.
    et al.
    University of Groningen, Netherlands .
    Damman, Kevin
    University of Groningen, Netherlands .
    Voors, Adriaan A.
    University of Groningen, Netherlands .
    van der Wal, Martje H.
    University of Groningen, Netherlands .
    Jaarsma, Tiny
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences.
    van Veldhuisen, Dirk J.
    University of Groningen, Netherlands .
    Hillege, Hans L.
    University of Groningen, Netherlands University of Groningen, Netherlands .
    Prognostic Value of Plasma Neutrophil Gelatinase-Associated Lipocalin for Mortality in Patients With Heart Failure2014In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 7, no 1, p. 35-42Article in journal (Refereed)
    Abstract [en]

    Background In patients with heart failure, renal dysfunction is associated with a poor outcome. We aimed to assess the prognostic value of plasma neutrophil gelatinase-associated lipocalin (NGAL), a novel marker of renal tubular damage, in patients with heart failure with or without renal dysfunction, and compare it with 2 frequently used biomarkers of chronic kidney disease. Methods and Results Plasma NGAL, estimated glomerular filtration rate (eGFR), and cystatin C were assessed in 562 patients with heart failure. Chronic kidney disease was defined as eGFRless than60 mL/min per 1.73 m(2). Outcome was all-cause mortality at 36 months. Mean age was 7111 years, 61% were men, and 97% were in New York Heart Association functional class II/III. Mean baseline eGFR was 54 +/- 20 mL/min per 1.73 m(2), mean cystatin C was 11.2 (7.7-16.2) mg/L, and median plasma NGAL was 85 (60-123) ng/mL. Higher plasma NGAL levels were independently associated with an increased risk of all-cause mortality, in patients with and without chronic kidney disease (hazard ratio [per SD increase in log NGAL]=1.45 [1.22-1.72]; Pless than0.001 and hazard ratio=1.51 [1.06-2.16]; P=0.023, respectively). Similarly, both in patients with high and low cystatin C (median cut-off), higher plasma NGAL levels were independently associated with an increased risk of all-cause mortality. Moreover, when NGAL was entered in the multivariable risk prediction model, eGFR (P=0.616) and cystatin C (P=0.937) were no longer associated with mortality. Conclusions Plasma NGAL predicts mortality in patients with heart failure, both in patients with and without chronic kidney disease and is a stronger predictor for mortality than the established renal function indices eGFR and cystatin C.

  • 10.
    Vedin, Ola
    et al.
    Uppsala University, Sweden; Uppsala Clin Research Centre, Sweden.
    Lam, Carolyn S. P.
    National Heart Centre Singapore, Singapore; Duke NUS Medical Sch, Singapore.
    Koh, Angela S.
    National Heart Centre Singapore, Singapore; Duke NUS Medical Sch, Singapore.
    Benson, Lina
    Regional Cancer Centre Stockholm Gotland, Sweden.
    Hwa Katherine Teng, Tiew
    National Heart Centre Singapore, Singapore; University of Western Australia, Australia.
    Ting Tay, Wan
    National Heart Centre Singapore, Singapore.
    Braun, Oscar O.
    Lund University, Sweden.
    Savarese, Gianluigi
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lund, Lars H.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Significance of Ischemic Heart Disease in Patients With Heart Failure and Preserved, Midrange, and Reduced Ejection Fraction A Nationwide Cohort Study2017In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 10, no 6, article id e003875Article in journal (Refereed)
    Abstract [en]

    Background-The pathogenic role of ischemic heart disease (IHD) in heart failure (HF) with reduced ejection fraction (HFrEF; EF amp;lt;40%) is well established, but its pathogenic and prognostic significance in HF with midrange (HFmrEF; EF 40%-50%) and preserved EF (HFpEF; EF amp;gt;= 50%) has been much less explored. Methods and Results-We evaluated 42 987 patients from the Swedish Heart Failure Registry with respect to baseline IHD, outcomes (IHD, HF, cardiovascular events, and all-cause death), and EF change during a median follow-up of 2.2 years. Overall, 23% had HFpEF (52% IHD), 21% had HFmrEF (61% IHD), and 55% had HFrEF (60% IHD). After multivariable adjustment, associations with baseline IHD were similar for HFmrEF and HFrEF and lower in HFpEF (risk ratio, 0.91 [0.89-0.93] versus HFmrEF and risk ratio, 0.90 [0.88-0.92] versus HFrEF). The adjusted risk of IHD events was similar for HFmrEF versus HFrEF and lower in HFpEF (hazard ratio, 0.89 [0.84-0.95] versus HFmrEF and hazard ratio, 0.84 [0.80-0.90] versus HFrEF). After adjustment, prevalent IHD was associated with increased risk of IHD events and all other outcomes in all EF categories except all-cause mortality in HFpEF. Those with IHD, particularly new IHD events, were also more likely to change to a lower EF category and less likely to change to a higher EF category over time. Conclusions-HFmrEF resembled HFrEF rather than HFpEF with regard to both a higher prevalence of IHD and a greater risk of new IHD events. Established IHD was an important prognostic factor across all HF types.

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