Heart Rate and Heart Failure With Preserved Ejection Fraction
2019; Lippincott Williams & Wilkins; Volume: 12; Issue: 8 Linguagem: Inglês
10.1161/circheartfailure.119.006213
ISSN1941-3297
AutoresMarkus Meyer, Martin M. LeWinter,
Tópico(s)Cardiac electrophysiology and arrhythmias
ResumoHomeCirculation: Heart FailureVol. 12, No. 8Heart Rate and Heart Failure With Preserved Ejection Fraction Free AccessArticle CommentaryPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessArticle CommentaryPDF/EPUBHeart Rate and Heart Failure With Preserved Ejection FractionTime to Slow β-Blocker Use? Markus Meyer, MD, PhD and Martin M LeWinter, MD Markus MeyerMarkus Meyer Cardiology Unit, Department of Medicine, Larner College of Medicine at the University of Vermont, Burlington. and Martin M LeWinterMartin M LeWinter Martin M. LeWinter, MD, Larner College of Medicine University of Vermont, UVMMC, McClure 1, Cardiology, 111 Colchester Ave, Burlington, Vermont 05401. Email E-mail Address: [email protected] Cardiology Unit, Department of Medicine, Larner College of Medicine at the University of Vermont, Burlington. Originally published1 Aug 2019https://doi.org/10.1161/CIRCHEARTFAILURE.119.006213Circulation: Heart Failure. 2019;12:e006213There is a widely held belief that pharmacological heart rate (HR) lowering provides patients with heart failure with preserved ejection fraction (HFpEF) a benefit because it results in more time for ventricular filling.1 This view seems to influence medication choices. In recent large HFpEF trials, about 80% of patients were receiving β-blockers.2 Some patients may have appropriate indications, for example, a mildly reduced EF. However, in many, the indication is hypertension, stable coronary artery disease, or atrial fibrillation, for which β-blockers are no longer considered a preferred long-term treatment and have an uncertain benefit. Our goal in this article is to discuss how changes in resting HR influence cardiac function, especially relaxation and filling, in large animals, normal human subjects and patients with HFpEF (defined based on EF ≥50%) and whether there is a role for pharmacological HR lowering in HFpEF. Because their daily activity levels are very low,3 we focus on resting HR as being most relevant to patients with HFpEF.Effects of Acute HR Changes in Normal Myocardium and the Intact Left VentricleThe effects of stimulation frequency on myocardial contraction and relaxation have been well-characterized in isolated human myocardium. Isometrically contracting normal myocardium displays an increase in systolic force up to 130 to 170/min, above which force declines. As frequency increases, the relaxation rate also increases. Under these fixed preload and afterload conditions, diastolic force eventually rises when the diastolic interval becomes so short that relaxation cannot be completed despite the increase in relaxation rate. These cumulative changes in contraction-relaxation dynamics are largely accounted for by cellular calcium handling.4,5There is limited in vivo information about how isolated increases in HR, usually produced by atrial pacing, affect contraction-relaxation dynamics in normal hearts. Findings from animal studies are that higher HRs reduce left ventricular (LV) end-diastolic pressure and accelerate contraction and relaxation, reflected in a higher dP/dt and a shortened τ (time constant of isovolumic pressure decline).6 Less well-recognized is the fact that LV diastolic and systolic dimensions progressively decrease at higher HRs. At very high HRs, this leads to stroke volumes that approach zero, a physiological response commonly used during transcatheter aortic valve replacement procedures.Results in normal human subjects generally parallel observations in large animals.7 With atrial pacing, LV diastolic and systolic volumes typically decrease while dP/dt and Ees, the slope of the end-systolic pressure-volume relation, an index of contractility, increase. Although not all studies report a decrease in τ, lower filling pressures have been a uniform finding at higher HRs.8 Between-study differences may be explained by the actual HRs used, loading conditions and neurohumoral background. The best approach to estimate τ is also a matter of debate.What accounts for observed changes in diastolic volumes and pressure with acute increases in HR in normal hearts? Smaller ES volumes at higher HRs can be explained by increased intracellular calcium levels,9 which move the systolic volume to a leftward-shifted, steeper end-systolic pressure-volume relation. Volume and pressure at the beginning of diastole are reduced and, all else being equal, the pressure remains reduced throughout diastole. At smaller systolic volumes, there is also an increase in elastic recoil including torsional deformation responsible for filling by suction and hence lower diastolic pressures. The decrease in end-diastolic volume at higher HRs is usually explained by shortening of the cardiac cycle primarily at the expense of diastole, with a decrease in time available for filling. However, this is likely not the whole story because the reduction in filling time most prominently affects mid-diastole or diastasis, when transmitral flow is at its lowest. Other contributors may include a preload-dependent decrease in the atrial contribution to filling and changes in afterload. In addition, it is conceivable that increased myocardial oxygen demand combined with reduced coronary flow at high HRs leads to ischemia, which could confound the effects of HR on volume and pressures. However, a loss in time available for coronary flow is typically overcome by coronary vasodilation.10 Conversely, it is also well documented that pharmacological HR lowering does not improve coronary arterial flow.11Effects of HR Changes in HFpEFThe hemodynamic effects of increasing HR to 120/min by atrial pacing in patients with HFpEF have been reported (Figure).8 Compared with resting HR, LV end-diastolic pressure strikingly decreased (from 17 to 8 mm Hg) at 120/min while end-diastolic, end-systolic, and stroke volumes all declined. Compared with control subjects, as HR increased the rise in dP/dt was blunted, but shortening of τ was preserved.Download figureDownload PowerPointFigure. Illustration of the acute effects of an increase in heart rate in heart failure with preserved ejection fraction.The acute hemodynamic effects of lower HRs in HFpEF have not been studied. Because LV end-diastolic pressure declines substantially with HR elevations in HFpEF, it is likely that slowing the resting HR will raise filling pressures. As increases in HR in patients with HFpEF are associated with LV volume reductions that result in a blunted HR—cardiac output relationship, slowing of resting HR will likely modestly reduce cardiac output.8 This, along with increased filling pressures, is obviously undesirable in patients with HFpEF and suggests that higher resting HRs might provide hemodynamic benefits.The potential benefits of higher HRs in HFpEF might be related to the level of basal contractility, assessed as systolic stiffness. For example, patients with very steep end-systolic pressure-volume relations, typified by some elderly women with HFpEF, would be expected to have a reduced capacity to shift this relationship leftward with increasing HR, that is, reduced contractile reserve, and thus smaller decreases in diastolic pressure and volume mediated by increased HR. If these patients also had higher basal relaxation rates (which we do not know), their ability to potentially speed relaxation further as a function of HR might also be limited.It is important to not confuse HR-induced changes produced by pacing with the much more complex changes that occur during exercise. Principal differences include increased adrenergic tone, which results in larger changes in contractility-relaxation dynamics, and the action of skeletal muscle pumps which increase systemic venous return. During exercise in normal subjects, these combine to maintain LV volumes with little change in filling pressure. In contrast, in patients with HFpEF filling pressure increases markedly.12 In addition, patients with HFpEF are reported to have a blunted HR response to exercise (chronotropic incompetence) that is further exacerbated by pharmacological HR lowering.13Chronic resting HR elevations have also not been studied in HFpEF. However, the guideline-influencing RACE II trial (Rate Control Efficacy in Permanent Atrial Fibrillation: a Comparison Between Lenient Versus Strict Rate Control II) trial provides insights into the chronic effects of higher HRs in patients with atrial fibrillation, who also frequently have hypertensive heart disease and diastolic dysfunction.14 This trial demonstrated that a more lenient HR control strategy of up to 110 per minutes was noninferior to a HR of 35% to define HFpEF. It enrolled 752 participants, approximately half with an EF 40% and did not detect any beneficial or adverse effects even after limiting the analysis to patients with EF ≥50%.21 However, the total daily dose of carvedilol averaged only 8.5 mg, which likely resulted in modest β-adrenergic blockade at best. Thus, it is unlikely that any definitive conclusions can be derived from these 2 trials that can be applied to patients with a modern, EF ≥50% definition of HFpEF.Ivabradine has little in the way of cardiovascular effects other than HR lowering. The functional effects of selective HR lowering with ivabradine in patients with HFpEF were evaluated in 2 studies.22,23 These studies were contradictory. The first22 found an improvement in functional capacity while the second23 demonstrated a reduction in exercise capacity. The only randomized, placebo-controlled, long-term outcomes trial of ivabradine in HFpEF, the EDIFY (Preserved Left Ventricular Ejection Fraction Chronic Heart Failure With Ivabradine Study) enrolled 179 patients with resting HRs above 70 bpm. An HR reduction of 8 per minutes failed to improve E/e′ ratio, walk distance or NT-proBNP levels in patients with HFpEF.24 Thus, pharmacological HR lowering with ivabradine does not appear to provide any consistent benefit in HFpEF. Last, it is concerning that in a much larger ivabradine trial in patients with coronary artery disease without heart failure a 20% increase in heart failure admissions was observed.25ConclusionsThe weight of evidence gleaned from normal subjects and patients with HFpEF indicates that within the physiological range, an acute increase in resting HR results in LV volume reduction and lower, not higher filling pressures. Moreover, we have argued elsewhere that pharmacological HR lowering in general in patients with normal EFs has adverse effects on exercise capacity and outcomes.26–28 Accordingly, it is our contention that pharmacological HR lowering almost certainly has no benefit in most patients with HFpEF and may well be deleterious. Nonetheless, there are selected indications for which pharmacological HR lowering is likely beneficial, including protection from excessive ventricular rates in atrial fibrillation, prophylaxis of tachyarrythmias and symptomatic treatment of effort angina, albeit with uncertain effects on long-term outcomes. For the specific case of rate control in atrial fibrillation, if the results of RACE-2 can indeed be extended to patients with HFpEF, a more lenient rate strategy may be indicated in these patients, with consideration given to weaning β-blockers and other rate-lowering drugs in selected cases. Such an approach should ideally be tested in a controlled fashion.With respect to β-blockers, considering the high prevalence of their use in HFpEF, it is unlikely that a large, definitive outcome trial can realistically be undertaken. A withdrawal trial may be the only practical way to test whether β-blockers have a role in HFpEF. For now—in light of a questionable rationale and an uncertain evidence basis—it is our belief that it is prudent to avoid the use of β-blockers in HFpEF in the absence of a clear and specific indication.Sources of FundingThis research was supported by National Institutes of Health grants R01 HL-118524 (Dr LeWinter) and R01 HL-122744 (Dr Meyer).DisclosuresDr Meyer and the University of Vermont have licensed patents for the use of pacemakers for the prevention and treatment of heart failure with preserved ejection fraction. The other author reports no conflicts.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Martin M. LeWinter, MD, Larner College of Medicine University of Vermont, UVMMC, McClure 1, Cardiology, 111 Colchester Ave, Burlington, Vermont 05401. Email martin.[email protected]orgReferences1. Topol EJ, Traill TA, Fortuin NJ. Hypertensive hypertrophic cardiomyopathy of the elderly.N Engl J Med. 1985; 312:277–283. doi: 10.1056/NEJM198501313120504CrossrefMedlineGoogle Scholar2. Solomon SD, Rizkala AR, Lefkowitz MP, Shi VC, Gong J, Anavekar N, Anker SD, Arango JL, Arenas JL, Atar D, Ben-Gal T, Boytsov SA, Chen CH, Chopra VK, Cleland J, Comin-Colet J, Duengen HD, Echeverría Correa LE, Filippatos G, Flammer AJ, Galinier M, Godoy A, Goncalvesova E, Janssens S, Katova T, Køber L, Lelonek M, Linssen G, Lund LH, O'Meara E, Merkely B, Milicic D, Oh BH, Perrone SV, Ranjith N, Saito Y, Saraiva JF, Shah S, Seferovic PM, Senni M, Sibulo AS, Sim D, Sweitzer NK, Taurio J, Vinereanu D, Vrtovec B, Widimský J, Yilmaz MB, Zhou J, Zweiker R, Anand IS, Ge J, Lam CSP, Maggioni AP, Martinez F, Packer M, Pfeffer MA, Pieske B, Redfield MM, Rouleau JL, Van Veldhuisen DJ, Zannad F, Zile MR, McMurray JJV. Baseline characteristics of patients with heart failure and preserved ejection fraction in the PARAGON-HF Trial.Circ Heart Fail. 2018; 11:e004962. doi: 10.1161/CIRCHEARTFAILURE.118.004962LinkGoogle Scholar3. Snipelisky D, Kelly J, Levine JA, Koepp GA, Anstrom KJ, McNulty SE, Zakeri R, Felker GM, Hernandez AF, Braunwald E, Redfield MM. Accelerometer-measured daily activity in heart failure with preserved ejection fraction: clinical correlates and association with standard heart failure severity indices.Circ Heart Fail. 2017; 10:e003878. doi: 10.1161/CIRCHEARTFAILURE.117.003878LinkGoogle Scholar4. Pieske B, Kretschmann B, Meyer M, Holubarsch C, Weirich J, Posival H, Minami K, Just H, Hasenfuss G. Alterations in intracellular calcium handling associated with the inverse force-frequency relation in human dilated cardiomyopathy.Circulation. 1995; 92:1169–1178.LinkGoogle Scholar5. Runte KE, Bell SP, Selby DE, Häußler TN, Ashikaga T, LeWinter MM, Palmer BM, Meyer M. Relaxation and the role of calcium in isolated contracting myocardium from patients with hypertensive heart disease and heart failure with preserved ejection fraction.Circ Heart Fail. 2017; 10:e004311. doi: 10.1161/CIRCHEARTFAILURE.117.004311LinkGoogle Scholar6. Karliner JS, LeWinter MM, Mahler F, Engler R, O'Rourke RA. Pharmacologic and hemodynamic influences on the rate of isovolumic left ventricular relaxation in the normal conscious dog.J Clin Invest. 1977; 60:511–521. doi: 10.1172/JCI108803CrossrefMedlineGoogle Scholar7. Wainstein RV, Sasson Z, Mak S. Frequency-dependent left ventricular performance in women and men.Am J Physiol Heart Circ Physiol. 2012; 302:H2363–H2371. doi: 10.1152/ajpheart.01125.2011CrossrefMedlineGoogle Scholar8. Wachter R, Schmidt-Schweda S, Westermann D, Post H, Edelmann F, Kasner M, Lüers C, Steendijk P, Hasenfuss G, Tschöpe C, Pieske B. Blunted frequency-dependent upregulation of cardiac output is related to impaired relaxation in diastolic heart failure.Eur Heart J. 2009; 30:3027–3036. doi: 10.1093/eurheartj/ehp341CrossrefMedlineGoogle Scholar9. Selby DE, Palmer BM, LeWinter MM, Meyer M. Tachycardia-induced diastolic dysfunction and resting tone in myocardium from patients with a normal ejection fraction.J Am Coll Cardiol. 2011; 58:147–154. doi: 10.1016/j.jacc.2010.10.069CrossrefMedlineGoogle Scholar10. Duncker DJ, Bache RJ. Regulation of coronary blood flow during exercise.Physiol Rev. 2008; 88:1009–1086. doi: 10.1152/physrev.00045.2006CrossrefMedlineGoogle Scholar11. Nayler WG, Carson V. Effect of stellate ganglion stimulation on myocardial blood flow, oxygen consumption, and cardiac efficiency during beta-adrenoceptor blockade.Cardiovasc Res. 1973; 7:22–29. doi: 10.1093/cvr/7.1.22CrossrefMedlineGoogle Scholar12. Borlaug BA, Nishimura RA, Sorajja P, Lam CS, Redfield MM. Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction.Circ Heart Fail. 2010; 3:588–595. doi: 10.1161/CIRCHEARTFAILURE.109.930701LinkGoogle Scholar13. Borlaug BA, Melenovsky V, Russell SD, Kessler K, Pacak K, Becker LC, Kass DA. Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction.Circulation. 2006; 114:2138–2147. doi: 10.1161/CIRCULATIONAHA.106.632745LinkGoogle Scholar14. Van Gelder IC, Groenveld HF, Crijns HJ, Tuininga YS, Tijssen JG, Alings AM, Hillege HL, Bergsma-Kadijk JA, Cornel JH, Kamp O, Tukkie R, Bosker HA, Van Veldhuisen DJ, Van den Berg MP; RACE II Investigators. Lenient versus strict rate control in patients with atrial fibrillation.N Engl J Med. 2010; 362:1363–1373. doi: 10.1056/NEJMoa1001337CrossrefMedlineGoogle Scholar15. Luchner A, Burnett JC, Jougasaki M, Hense HW, Riegger GA, Schunkert H. Augmentation of the cardiac natriuretic peptides by beta-receptor antagonism: evidence from a population-based study.J Am Coll Cardiol. 1998; 32:1839–1844.CrossrefMedlineGoogle Scholar16. Conraads VM, Metra M, Kamp O, De Keulenaer GW, Pieske B, Zamorano J, Vardas PE, Böhm M, Dei Cas L. Effects of the long-term administration of nebivolol on the clinical symptoms, exercise capacity, and left ventricular function of patients with diastolic dysfunction: results of the ELANDD study.Eur J Heart Fail. 2012; 14:219–225. doi: 10.1093/eurjhf/hfr161CrossrefMedlineGoogle Scholar17. Edelmann F, Musial-Bright L, Gelbrich G, et al. Tolerability and feasibility of beta-blocker titration in HFpEF versus HFrEF: Insights from the CIBIS-ELD Trial.JACC Heart Fail. 2016; 4:140–149.CrossrefMedlineGoogle Scholar18. Bergström A, Andersson B, Edner M, Nylander E, Persson H, Dahlström U. Effect of carvedilol on diastolic function in patients with diastolic heart failure and preserved systolic function. Results of the Swedish doppler-echocardiographic study (SWEDIC).Eur J Heart Fail. 2004; 6:453–461. doi: 10.1016/j.ejheart.2004.02.003CrossrefMedlineGoogle Scholar19. Flather MD, Shibata MC, Coats AJ, Van Veldhuisen DJ, Parkhomenko A, Borbola J, Cohen-Solal A, Dumitrascu D, Ferrari R, Lechat P, Soler-Soler J, Tavazzi L, Spinarova L, Toman J, Böhm M, Anker SD, Thompson SG, Poole-Wilson PA; SENIORS Investigators. Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS).Eur Heart J. 2005; 26:215–225. doi: 10.1093/eurheartj/ehi115CrossrefMedlineGoogle Scholar20. Cleland JGF, Bunting KV, Flather MD, Altman DG, Holmes J, Coats AJS, Manzano L, McMurray JJV, Ruschitzka F, van Veldhuisen DJ, von Lueder TG, Böhm M, Andersson B, Kjekshus J, Packer M, Rigby AS, Rosano G, Wedel H, Hjalmarson Å, Wikstrand J, Kotecha D; Beta-blockers in Heart Failure Collaborative Group. Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: an individual patient-level analysis of double-blind randomized trials.Eur Heart J. 2018; 39:26–35. doi: 10.1093/eurheartj/ehx564CrossrefMedlineGoogle Scholar21. Yamamoto K, Origasa H, Hori M; J-DHF Investigators. Effects of carvedilol on heart failure with preserved ejection fraction: the japanese diastolic heart failure study (J-DHF).Eur J Heart Fail. 2013; 15:110–118. doi: 10.1093/eurjhf/hfs141CrossrefMedlineGoogle Scholar22. Kosmala W, Holland DJ, Rojek A,Wright L, Przewlocka-Kosmala M, Marwick TH. Effect of I f-channel inhibition on hemodynamic status and exercise tolerance in heart failure with preserved ejection fraction: a randomized trial.J Am Coll Cardiol. 2013; 62:1330–1338. doi:10.1016/j.jacc.2013.06.043CrossrefMedlineGoogle Scholar23. Pal N, Sivaswamy N, Mahmod M, Yavari A, Rudd A, Singh S, Dawson DK, Francis JM, Dwight JS, Watkins H, Neubauer S, Frenneaux M, Ashrafian H. Effect of selective heart rate slowing in heart failure with preserved ejection fraction.Circulation. 2015; 132:1719–1725. doi: 10.1161/CIRCULATIONAHA.115.017119LinkGoogle Scholar24. Komajda M, Isnard R, Cohen-Solal A, Metra M, Pieske B, Ponikowski P, Voors AA, Dominjon F, Henon-Goburdhun C, Pannaux M, Böhm M; prEserveD left ventricular ejectIon fraction chronic heart Failure with ivabradine studY (EDIFY) Investigators. Effect of ivabradine in patients with heart failure with preserved ejection fraction: the EDIFY randomized placebo-controlled trial.Eur J Heart Fail. 2017; 19:1495–1503. doi: 10.1002/ejhf.876CrossrefMedlineGoogle Scholar25. Fox K, Ford I, Steg PG, Tardif JC, Tendera M, Ferrari R; SIGNIFY Investigators. Ivabradine in stable coronary artery disease without clinical heart failure.N Engl J Med. 2014; 371:1091–1099. doi: 10.1056/NEJMoa1406430CrossrefMedlineGoogle Scholar26. Meyer M, Rambod M, LeWinter M. Pharmacological heart rate lowering in patients with a preserved ejection fraction-review of a failing concept.Heart Fail Rev. 2018; 23:499–506. doi: 10.1007/s10741-017-9660-1CrossrefMedlineGoogle Scholar27. Nambiar L, Meyer M. β-Blockers in myocardial infarction and coronary artery disease with a preserved ejection fraction: recommendations, mechanisms, and concerns.Coron Artery Dis. 2018; 29:262–270. doi: 10.1097/MCA.0000000000000610CrossrefMedlineGoogle Scholar28. Epstein S, Robinson BF, Kahler RL, Braunwald E. Effects of beta-adrenergic blockade on the cardiac response to maximal and submaximal exercise in man.J Clin Invest. 1965; 44:1745–1753. doi: 10.1172/JCI105282CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited ByKagami K, Obokata M, Harada T, Kato T, Wada N, Adachi T and Ishii H (2022) Diastolic Filling Time, Chronotropic Response, and Exercise Capacity in Heart Failure and Preserved Ejection Fraction With Sinus Rhythm, Journal of the American Heart Association, 11:13, Online publication date: 5-Jul-2022. Infeld M, Wahlberg K, Cicero J, Meagher S, Habel N, Muthu Krishnan A, Silverman D, Lustgarten D and Meyer M (2022) Personalized pacing for diastolic dysfunction and heart failure with preserved ejection fraction: Design and rationale for the myPACE randomized controlled trial, Heart Rhythm O2, 10.1016/j.hroo.2021.11.015, 3:1, (109-116), Online publication date: 1-Feb-2022. Silverman D, de Lavallaz J, Plante T, Infeld M, Goyal P, Juraschek S, Dougherty G, Callas P and Meyer M (2022) Beta-Blocker Use in Hypertension and Heart Failure (A Secondary Analysis of the Systolic Blood Pressure Intervention Trial), The American Journal of Cardiology, 10.1016/j.amjcard.2021.10.049, 165, (58-64), Online publication date: 1-Feb-2022. Camafort M, Valdez-Tiburcio O and Wyss F (2022) Hypertension and heart failure with preserved ejection fraction. A past, present, and future relationship, Hipertensión y Riesgo Vascular, 10.1016/j.hipert.2021.12.003, 39:1, (34-41), Online publication date: 1-Jan-2022. Song P, Kim M, Seong S, Park J, Choi S, Hahn J, Gwon H, Hur S, Rha S, Yoon C, Jeong M, Seong I and Jeong J (2021) Heart failure with mid-range ejection fraction and the effect of β-blockers after acute myocardial infarction, Heart and Vessels, 10.1007/s00380-021-01876-1, 36:12, (1848-1855), Online publication date: 1-Dec-2021. Palau P, Seller J, Domínguez E, Sastre C, Ramón J, de La Espriella R, Santas E, Miñana G, Bodí V, Sanchis J, Valle A, Chorro F, Llácer P, Bayés-Genís A and Núñez J (2021) Effect of β-Blocker Withdrawal on Functional Capacity in Heart Failure and Preserved Ejection Fraction, Journal of the American College of Cardiology, 10.1016/j.jacc.2021.08.073, 78:21, (2042-2056), Online publication date: 1-Nov-2021. Meyer M, Du Fay Lavallaz J, Benson L, Savarese G, Dahlström U and Lund L (2021) Association Between β-Blockers and Outcomes in Heart Failure With Preserved Ejection Fraction: Current Insights From the SwedeHF Registry, Journal of Cardiac Failure, 10.1016/j.cardfail.2021.04.015, 27:11, (1165-1174), Online publication date: 1-Nov-2021. Kasiakogias A, Rosei E, Camafort M, Ehret G, Faconti L, Ferreira J, Brguljan J, Januszewicz A, Kahan T, Manolis A, Tsioufis K, Weber T, von Lueder T, Smiseth O, Wachtell K, Kjeldsen S, Zannad F, Mancia G and Kreutz R (2021) Hypertension and heart failure with preserved ejection fraction: position paper by the European Society of Hypertension, Journal of Hypertension, 10.1097/HJH.0000000000002910, 39:8, (1522-1545), Online publication date: 1-Aug-2021. Shchendrygina A, Zhbanov K, Privalova E, Yusupova A, Danilogorskaya Y, Salakheeva E, Sokolova I, Tsatsurova S, Ageeva A and Belenkov Y (2021) Heart Failure with Perserved Ejection Fraction Current Diagnostic and Therapeutic Approaches, Rational Pharmacotherapy in Cardiology, 10.20996/1819-6446-2021-05-01, 17:3, (476-483) Navid P, Nguyen L, Jaber D, Zarzuela K, Musse M, Lu Wang M, Requijo T, Kozlov E, Masterson Creber R, Hilmer S, Lachs M and Goyal P (2021) Attitudes toward deprescribing among adults with heart failure with preserved ejection fraction, Journal of the American Geriatrics Society, 10.1111/jgs.17204, 69:7, (1948-1955), Online publication date: 1-Jul-2021. Bistola V, Simitsis P, Parissis J, Ouwerkerk W, Veldhuisen D, Cleland J, Anker S, Samani N, Metra M, Zannad F, Polyzogopoulou E, Keramida K, Farmakis D, Voors A and Filippatos G (2021) Association between up‐titration of medical therapy and total hospitalizations and mortality in patients with recent worsening heart failure across the ejection fraction spectrum, European Journal of Heart Failure, 10.1002/ejhf.2219, 23:7, (1170-1181), Online publication date: 1-Jul-2021. Dunkley J, Irion C, Yousefi K, Shehadeh S, Lambert G, John-Williams K, Webster K, Goldberger J and Shehadeh L (2021) Carvedilol and exercise combination therapy improves systolic but not diastolic function and reduces plasma osteopontin in Col4a3 −/− Alport mice , American Journal of Physiology-Heart and Circulatory Physiology, 10.1152/ajpheart.00535.2020, 320:5, (H1862-H1872), Online publication date: 1-May-2021. Brinker L, Konerman M, Navid P, Dorsch M, McNamara J, Willer C, Tinetti M, Hummel S and Goyal P (2021) Complex and Potentially Harmful Medication Patterns in Heart Failure with Preserved Ejection Fraction, The American Journal of Medicine, 10.1016/j.amjmed.2020.07.023, 134:3, (374-382), Online publication date: 1-Mar-2021. Conceição L, Gois C, Fernandes R, Souza D, Júnior M and Carvalho V (2020) Effect of ivabradine on exercise capacity in individuals with heart failure with preserved ejection fraction, Heart Failure Reviews, 10.1007/s10741-020-10002-8, 26:1, (157-163), Online publication date: 1-Jan-2021. Infeld M, Avram R, Wahlberg K, Silverman D, Habel N, Lustgarten D, Pletcher M, Olgin J, Marcus G and Meyer M (2020) An approach towards individualized lower rate settings for pacemakers, Heart Rhythm O2, 10.1016/j.hroo.2020.09.004, 1:5, (390-393), Online publication date: 1-Dec-2020. Palau P, Domínguez E, Seller J, Sastre C, Bayés-Genís A and Núñez J (2020) Chronotropic Incompetence Predicts Distance Walked in Six-Minute Walk Test in Heart Failure With Preserved Ejection Fraction, Journal of Cardiac Failure, 10.1016/j.cardfail.2020.08.011, 26:11, (1024-1025), Online publication date: 1-Nov-2020. Cui X, Thunström E, Dahlström U, Zhou J, Ge J and Fu M (2020) Trends in cause‐specific readmissions in heart failure with preserved vs. reduced and mid‐range ejection fraction, ESC Heart Failure, 10.1002/ehf2.12899, 7:5, (2894-2903), Online publication date: 1-Oct-2020. Silverman D, Rambod M, Lustgarten D, Lobel R, LeWinter M and Meyer M (2020) Heart Rate–Induced Myocardial Ca2+ Retention and Left Ventricular Volume Loss in Patients With Heart Failure With Preserved Ejection Fraction, Journal of the American Heart Association, 9:17, Online publication date: 1-Sep-2020. Kokhan E, Kiyakbaev G and Kobalava Z (2020) Frequency of use and Indications for Beta-Blockers in Heart Failure with Preserved Ejection Fraction, Kardiologiia, 10.18087/cardio.2020.6.n1062, 60:6, (30-40) Kim M and Park S (2020) Heart failure with preserved ejection fraction: insights from recent clinical researches, The Korean Journal of Internal Medicine, 10.3904/kjim.2020.104, 35:3, (514-534), Online publication date: 1-May-2020. Formiga F, Palau P and Nuñez J (2020) Betabloqueantes en la insuficiencia cardiaca con fracción de eyección preservada: ¿prescribir o deprescribir?, Revista Española de Geriatría y Gerontología, 10.1016/j.regg.2020.01.003, 55:3, (129-130), Online publication date: 1-May-2020. Palau P, Seller J, Domínguez E, Gómez I, Ramón J, Sastre C, Espriella R, Santas E, Miñana G, Chorro F, González‐Juanatey J and Núñez J (2020) Beta‐blockers withdrawal in patients with heart failure with preserved ejection fraction and chronotropic incompetence: Effect on functional capacity rationale and study design of a prospective, randomized, controlled trial (The Preserve‐HR trial), Clinical Cardiology, 10.1002/clc.23345, 43:5, (423-429), Online publication date: 1-May-2020. (2020) Metoprolol for the Prevention of Exacerbations of COPD, New England Journal of Medicine, 10.1056/NEJMc2000638, 382:14, (1374-1376), Online publication date: 2-Apr-2020. Nambiar L, Silverman D, Vanburen P, LeWinter M and Meyer M (2020) Beta-Blocker Cessation in Stable Outpatients With Heart Failure With a Preserved Ejection Fraction, Journal of Cardiac Failure, 10.1016/j.cardfail.2019.08.020, 26:3, (281-282), Online publication date: 1-Mar-2020. Goyal P, Requijo T, Siceloff B, Shen M, Masterson Creber R, Hilmer S, Kronish I, Lachs M and Safford M (2019) Patient-Reported Barriers and Facilitators to Deprescribing Cardiovascular Medications, Drugs & Aging, 10.1007/s40266-019-00729-x, 37:2, (125-135), Online publication date: 1-Feb-2020. Ahn M, Yoo B, Son J, Yu M, Kang D, Lee H, Jeon E, Kim J, Chae S, Baek S, Kang S, Choi D, Kim K, Cho M and Kim S (2020) Beta-blocker Therapy at Discharge in Patients with Acute Heart Failure and Atrial Fibrillation, Journal of Korean Medical Science, 10.3346/jkms.2020.35.e278, 35:33 Silverman D, Plante T, Infeld M, Callas P, Juraschek S, Dougherty G and Meyer M (2019) Association of β-Blocker Use With Heart Failure Hospitalizations and Cardiovascular Disease Mortality Among Patients With Heart Failure With a Preserved Ejection Fraction, JAMA Network Open, 10.1001/jamanetworkopen.2019.16598, 2:12, (e1916598) Packer M (2019) Heightened risk of intensive rate control in patients with atrial fibrillation who are obese or have type 2 diabetes: A critical review and re‐evaluation, Journal of Cardiovascular Electrophysiology, 10.1111/jce.14236, 30:12, (3020-3024), Online publication date: 1-Dec-2019. August 2019Vol 12, Issue 8 Advertisement Article InformationMetrics © 2019 American Heart Association, Inc.https://doi.org/10.1161/CIRCHEARTFAILURE.119.006213PMID: 31525068 Originally publishedAugust 1, 2019 Keywordsatrial fibrillationheart rateheart failurebeta blockershypertensionPDF download Advertisement SubjectsCalcium Cycling/Excitation-Contraction CouplingContractile FunctionHeart FailureHemodynamicsPathophysiology
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