left ventricular diastolic dysfunction; heart failure with preserved ejection fraction (HFpEF)
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Etiology
- common causes
- hypertension, especially systolic hypertension (most common cause)[3]
- ischemic heart disease
- aortic stenosis
- less common causes
- risk factors*
* implantable defibrillator is a negative risk factor[34]
Epidemiology
- most common form of heart failure in the elderly[34]
- 55% of patients with heart failure[15]
- incidence increases with age
- slightly more common in obese patients
- less common in blacks than whites[34]
- 31-47% of patients hospitalized with heart failure[8]
- more common in women than men (4:1)[7]
Pathology
- inability of the left ventricle to fill normally during diastole
- decreased compliance of the ventricle walls
- LV ejection fraction is generally normal
- elevated pressures required for ventricular filling
- elevated pulmonary capillary pressure with pulmonary congestion may occur (diastolic heart failure)
- reduced left ventricular filling volume leads to lowered stroke volumes & symptoms of poor cardiac output
- shift in filling pattern to later in diastole, with increased dependence on atrial kick
- compensatory left atrial enlargement predisposes to atrial fibrillation
- pulmonary edema
- left heart failure leads to right heart failure
- poor nitric oxide availability suggested to play a role[50]
Clinical manifestations
- hypertension is present in 60% of patients with left ventricular diastolic dysfunction
- exertional dyspnea & progressive exercise intolerance[63]
- signs of right-sided heart failure
- acute diastolic dysfunction may result in pulmonary edema
- pulmonary edema more likely than peripheral edema with 1st episode of heart failure[64]
- orthostatic hypotension may result from reduced stroke volume with increase in heart rate
- wheezing may occur
- poor exercise capacity
- S4 heart sound
- bradycardia common[37]
Laboratory
- serum B-type natriuretic peptide (serum BNP) may be elevated[7]
- useful for establishing cardiac vs non-cardiac causes of dyspnea
- caution: serum BNP increases with age
- caution: serum BNP may be normal, particularly in obese or patients with dyspnea on exertion only[40]
- confirm heart failure with serum BNP prior to other workup (GRS11)[24]
- urine proteins associated with decreased risk of hospitalization for heart failure & for death include:
- angiopoietin-like protein 2 (ANGPTL2) RR=0.57
- alpha amylase 2A (AMY2A) RR=0.55
- deoxyribonuclease-1 (DNASE1) RR=0.57[71]
- higher urinary levels of proteins involved the following processes portend a lower risk of death or hopsitalization for heart failure:
- fibrosis (collagen VI alpha-1, collagen XV alpha-1
- metabolism (pancreatic alpha-amylase 2A/B, mannosidase alpha class 1A member 1
- inflammation (heat shock protein family D member 1, inducible T cell costimulatory ligand)[71]
Diagnostic procedures
- electrocardiogram
- left ventricular hypertrophy
- left atrial enlargement
- low voltage may be seen with cardiac amyloidosis
- echocardiogram (diagnostic procedure of choice)
- LV ejection fraction > 40-50%[24]; > 50%[3]
- LV ejection fraction > 60% common with 1st episode of heart failure
- decreased LV end-diastolic volume
- non-dilated, normally contracting myocardium
- left ventricular hypertrophy
- reveals presence & severity of outflow obstruction
- reversal of normal left ventricular diastolic trans- mitral inflow pattern (E/A < 1.0)*
- left atrial enlargement
- elevated filling pressures
- normal physiologic dependence on late, active filling with increasing age
- LV ejection fraction > 40-50%[24]; > 50%[3]
- H2FPEF risk score for patients presenting with dyspnea
- exclusion of coronary artery disease (CAD)
- right heart catheterization if indeterminate noninvasive testing or evidence of pulmonary hypertension[40]
- increased dependence of LV filling on atrial contraction
Complications
- congestive heart failure (with normal systolic function)
- increased risk of mortality 3.5 fold[5][15]
- despite increase in mortality, death from heart failure is rare
- syncope in association with tachycardia
- especially with paroxysmal atrial fibrillation
- loss of atrial kick -> reduced left ventricular filling
- diminished stroke volume & cardiac output
- especially with paroxysmal atrial fibrillation
- pulmonary hypertension
- pulmonary venous hypertension, pulmonary edema
- pulmonary hypertension associated with 24% 1 year mortality & 48% 5 year mortality[48]
- independent predictor of mortality[6][8]
- sudden cardiac death accounts for ~25-30% of deaths in clinical trials[43]
- hospitalized patients with LV diastolic dysfunction discharged with systolic BP < 120 mm Hg at significantly higher risk of 30-day, 1-year, & long-term all-cause mortality[47]
- comorbidities interacting adversely with HFpEF
Differential diagnosis
- pericardial disease
- transthyretin cardiac amyloidosis
- restrictive cardiomyopathy
- right heart failure, peripheral congestion
- infiltrative heart disease on echocardiogram
- restrictive filling pattern
- biatrial enlargement[68]
Management
- goals of therapy
- reduce the state of cardiopulmonary congestion
- reduce volume overload
- maintain atrial contraction
- decrease heart rate
- prevent/treat myocardial ischemia
- control hypertension, target systolic BP < 130 mm Hg[3]
- no difference in hospital readmission or mortality in patients with systolic BP > 130 mm Hg vs < 130 mm Hg[57]
- systolic BP <120 mm Hg associated with poor outcomes[57]
- attenuate neurohormonal activation
- prevent pulmonary fibrosis
- improve ventricular relaxation
- reduce the state of cardiopulmonary congestion
- pharmacologic agents
- SGLT-2 inhibitor (flozin) indicated[3][66]
- empagliflozin, dapagliflozin[62]
- lower risk for hospitalization for heart failure[3][72]
- flozins may improve maximal exercise capacity & quality of life in patients with heart failure HFrEF or HFpEF[70]
- semaglutide improves symptoms of obesity-related heart failure[69]
- little evidence of improved outcomes other than flozins or GLP-1 agonists[24][40]
- diuretics for volume overload
- increase current diuretic (preferably loop diuretic) for volume overload
- loop diuretics reduce HF hospitalization
- intravenous diuretic for patient not responding to escalating oral diuretic[68]
- spironolactone (antifibrotic?)
- not associated with clinical improvement[26][31][41]
- improves diastolic function & quality of life[24][59]
- reduces hospitalization in patients with increased serum BNP[24][59]
- may have mortality benefit for women[51]
- not all loop diuretics may be equal[41]
- longer-acting chlorthalidone may be more effective than HCTZ[24]
- may reduce LVH (8%[7])
- increase current diuretic (preferably loop diuretic) for volume overload
- beta blockers
- theoretically beneficial for symptomatic disease
- decrease myocardial oxygen demand
- diminish heart rate with increase of LV filling
- may promote regression of LVH (6%)[7])
- NO evidence to support a favorable influence on natural course of disease[41]
- marginal reduction in early mortality (18% vs 20%)
- only metoprolol succinate, carvedilol & bisoprolol reduce mortality[3]
- reduction in mortality & hospitalization, but not statistically significant[20]
- do NOT enhance myocardial relaxation
- bradycardia complicates titration of beta-blocker[37]
- theoretically beneficial for symptomatic disease
- renin-angiotensin system antagonists
- reduce HF hospitalization [71
- angiotensin converting enzyme (ACE) inhibitors
- may reduce LVH (10%[7][14]
- equivocal benefit on mortality & hospitalization for heart failure[32]
- mortality benefit only in patients with chronic renal failure (GFR < 45 L/min/1.73 m2) (RR = 0.81)[33]
- angiotensin receptor antagonist (ARB)
- may reduce LVH (13%[7])
- irbesartan fails to improve outcomes (death, hospitalization for cardiovascular events)[17][21]
- may reduce LVH (13%[7])
- may improve all-cause mortality[25], no effect on mortality[72]
- ACE inhibitors & ARBS have not improved prognosis in clinical trials[41]
- useful to control hypertension in patients on diuretic
- sacubitril/valsartan (ARNI) may be better than ACE inhibitor[52]
- reduces cardiovascular & renal events in patients with mild HFrEF or HFpEF[67]
- calcium channel blockers
- verapamil & diltiazem improve indices of LV diastolic dysfunction
- may reduce LVH (11%[7])
- reserve for patients intolerant of beta-blockers[3]
- nitrates
- nebulized inorganic sodium nitrite* TID of no benefit
- digoxin of no benefit[13]
- lowering blood pressure improves LV diastolic dysfunction regardless of drug type[16]
- sildenafil of no benefit[27]
- beta-blockers, ACE inhibitors, ARBs, or calcium-channel blockers may be effective in lowering blood pressure[36]
- any drug class that improves LV diastolic dysfunction reduces hospitalization (14% vs 16% with placebo), number needed to treat = 64[46]
- no individual medication class yields significant improvements[46]
- benefit of any agent unproven[24]
- limitations of one-size-fits all approach may give rise to personalized medicine approach[44]
- SGLT-2 inhibitor (flozin) indicated[3][66]
- other measures
- salt restriction
- adding any salt to cooking lowers risk for cardiovascular events & hospitalization for heart failure[61]
- unclear whether participants in study were taking spironolactone
- adding any salt to cooking lowers risk for cardiovascular events & hospitalization for heart failure[61]
- renal dialysis
- metoprolol (dialyzable) but not carvedilol (poorly dialyzable) reduces mortality during the first 6 months of renal dialysis when LVEF > 40% (RR=0.68)[58]
- plasmapheresis
- cardioversion for atrial fibrillation
- sequential AV pacing
- measures for ischemia
- coronary artery bypass surgery
- angioplasty
- radiofrequecy ablation of accessory conduction tract
- endurance exercise is effective in improving peak oxygen consumption[56]
- exercise & calorie restriction in obese patients to achieve weight reduction improves exercise capacity[38]
- high-intensity interval exercise no better than continous moderate intensity exercise in patients with HFpEF[56]
- extra virgin olive oil improves cardiopulmonary exercise testing[54]
- anticoagulation fails to provide a substantial benefit
- reduces risk of stroke at cost of increased bleeding[53]
- salt restriction
- investigational
- GDF11 reverses LV diastolic dysfunction in mice[28]
- follow-up after hospitalization or emergency department visit for heart failure
- see heart failure
* rationale is that poor nitric oxide availability may play role in LV diastolic dysfunction[50]
More general terms
Additional terms
- aortic valvular stenosis (AS)
- echocardiography
- hypertension (HTN, high blood pressure, HBP)
- hypertensive heart disease
- hypertrophic cardiomyopathy (HCM), including idiopathic hypertrophic subaortic stenosis (IHSS)
- left ventricular hypertrophy (LVH)
- restrictive cardiomyopathy
- transthyretin cardiac amyloidosis; amyloid transthyretin cardiomyopathy (ATTR-CM)
References
- ↑ nlmpubs.nlm.nih.gov/hstat/ahcpr/
- ↑ Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 1296
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 16, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2012, 2018, 2022
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ Watson K, in: UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
- ↑ 5.0 5.1 Gottdiener JS et al Outcome of congestive heart failure in elderly persons: influence of left ventricular systolic function. The Cardiovascular Health Study. Ann Intern Med 137:631, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12379062
- ↑ 6.0 6.1 Redfield MM et al Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA 289:194, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12517230
- ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 7.7 UpToDate version 12.2
- ↑ 8.0 8.1 8.2 Bhatia RS et al, Outcome of heart failure with preserved ejection fraction in a population-based study. N Engl J Med 2006; 355:260 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16855266
- ↑ 9.0 9.1 Lee DS, Pencina MJ, Benjamin EJ, Wang TJ, Levy D, O'Donnell CJ, Nam BH, Larson MG, D'Agostino RB, Vasan RS. Association of parental heart failure with risk of heart failure in offspring. N Engl J Med. 2006 Jul 13;355(2):138-47. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16837677
- ↑ Bhatia RS, Tu JV, Lee DS, Austin PC, Fang J, Haouzi A, Gong Y, Liu PP. Outcome of heart failure with preserved ejection fraction in a population-based study. N Engl J Med. 2006 Jul 20;355(3):260-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16855266
- ↑ Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006 Jul 20;355(3):251-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16855265
- ↑ Aurigemma GP. Diastolic heart failure--a common and lethal condition by any name. N Engl J Med. 2006 Jul 20;355(3):308-10. No abstract available. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16855273 Aurigemma GP, Gaasch WH Diastolic Heart Failure N Engl J Med 2004; 351:1097-1105. September 9, 2004 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/15356307 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMcp022709
- ↑ 13.0 13.1 Ahmed A, Rich MW, Fleg JL, Zile MR, Young JB, Kitzman DW, Love TE, Aronow WS, Adams KF Jr, Gheorghiade M. Effects of digoxin on morbidity and mortality in diastolic heart failure: the ancillary digitalis investigation group trial. Circulation. 2006 Aug 1;114(5):397-403. Epub 2006 Jul 24. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16864724
- ↑ 14.0 14.1 Cleland JG et al, The perindopril in elderly people with chronic heart failure (PEP-CHF) study. Eur Hear J 2006, 27:2338 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16963472
McMurray J Renin angiotensin blockade in heart failure with preserved ejection fraction: The signal gets stronger. Eur Hear J 2006, 27:2257 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16963471 - ↑ 15.0 15.1 15.2 Bursi F et al, Systolic and diastolic heart failure in the community. JAMA 2006, 296:2209 http://jama.ama-assn.org/cgi/content/full/296/18/2209
Hildebrandt P, Systolic and nonsystolic heart failure: Equally serious threats JAMA 2006, 296:2259 http://jama.ama-assn.org/cgi/content/full/296/18/2259 - ↑ 16.0 16.1 Solomon SD et al. Effect of angiotensin receptor blockade and antihypertensive drugs on diastolic function in patients with hypertension and diastolic dysfunction: A randomised trial. Lancet 2007 Jun 23; 369:2079-87 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17586303
Ahmed A et al. VALIDD should not invalidate angiotensin-receptor blockers. Lancet 2007 Jun 23; 369:2053-4 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17586284 - ↑ 17.0 17.1 Massie BM et al. for the I-PRESERVE Investigators. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med 2008 Nov 11; [e-pub ahead of print] <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/19001508 <Internet> http://dx.doi.org/10.1056/NEJMoa0805450
- ↑ Prescriber's Letter 16(1): 2009 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=250126&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Grewal J et al. Left ventricular function and exercise capacity. JAMA 2009 Jan 21; 301:286. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19155455
- ↑ 20.0 20.1 van Veldhuisen DJ et al. Beta-blockade with nebivolol in elderly heart failure patients with impaired and preserved left ventricular ejection fraction: Data from SENIORS (Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors With Heart Failure). J Am Coll Cardiol 2009 Jun 9; 53:2150. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19497441
- ↑ 21.0 21.1 Zile MR et al. Mode of death in patients with heart failure and a preserved ejection fraction: Results from the Irbesartan in Heart Failure with Preserved Ejection Fraction Study (I-Preserve) trial. Circulation 2010 Mar 30; 121:1393. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20231531
- ↑ 22.0 22.1 22.2 Russo C et al. Effect of obesity and overweight on left ventricular diastolic function: A community-based study in an elderly cohort. J Am Coll Cardiol 2011 Mar 22; 57:1368. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21414533
- ↑ Kane GC et al. Progression of left ventricular diastolic dysfunction and risk of heart failure. JAMA 2011 Aug 24/31; 306:856. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21862747
- ↑ 24.0 24.1 24.2 24.3 24.4 24.5 24.6 24.7 Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010
Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016
Geriatric Review Syllabus, 10th edition (GRS10) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2019
Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022 - ↑ 25.0 25.1 Lund LH et al Association Between Use of Renin-Angiotensin System Antagonists and Mortality in Patients With Heart Failure and Preserved Ejection Fraction. JAMA. 2012;308(20):2108-2117 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23188027 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1456058
Fang JC. Heart failure therapy: What should clinicians believe? JAMA 2012 Nov 28; 308:2144. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23188032 - ↑ 26.0 26.1 Edelmann F et al Effect of Spironolactone on Diastolic Function and Exercise Capacity in Patients With Heart Failure With Preserved Ejection Fraction. The Aldo-DHF Randomized Controlled Trial. JAMA. 2013;309(8):781-791 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23443441 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1656252
Cleland JGF and Pellicori P Defining Diastolic Heart Failure and Identifying Effective Therapies. JAMA. 2013;309(8):825-826. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23443447 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1656233 - ↑ 27.0 27.1 Redfield MM et al Effect of Phosphodiesterase-5 Inhibition on Exercise Capacity and Clinical Status in Heart Failure With Preserved Ejection Fraction. A Randomized Clinical Trial. JAMA. 2013;():1-10. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23478662 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1663257
- ↑ 28.0 28.1 Loffredo FS et al. Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy. Cell 2013 May 9; 153:828 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23663781
- ↑ Paulus WJ, van Ballegoij JJ. Treatment of heart failure with normal ejection fraction: an inconvenient truth! J Am Coll Cardiol. 2010 Feb 9;55(6):526-37. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20152557
- ↑ Chen MA Heart failure with preserved ejection fraction in older adults. Am J Med. 2009 Aug;122(8):713-23 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19635270
- ↑ 31.0 31.1 Pitt B, Pfieffer MA, Assmann SF et al Spironolactone for Heart Failure with Preserved Ejection Fraction. N Engl J Med 2014; 370:1383-1392April 10, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24716680 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1313731
- ↑ 32.0 32.1 Mujib M, Patel K, Fonarow GC, et. al. Angiotensin-converting enzyme inhibitors and outcomes in heart failure and preserved ejection fraction. Am J Med. 2013;126:401-410. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23510948
- ↑ 33.0 33.1 Ahmed A, Rich MW, Zile M, et. al. Renin-angiotensin inhibition in diastolic heart failure and chronic kidney disease. Am J Med. 2013;126:150-161. PMID: https://www.ncbi.nlm.nih.gov/pubmed/2333144
- ↑ 34.0 34.1 34.2 34.3 Gurwitz JH, Magid DJ, Smith DH, et al. Contemporary prevalence and correlates of incident heart failure with preserved ejection fraction. Am J Med. 2013;126:393-400 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23499328
- ↑ Meyer T, Shih J, Aurigemma G. Heart failure with preserved ejection fraction (diastolic dysfunction). Ann Intern Med. 2013;158(1):ITC1-1. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23277912
- ↑ 36.0 36.1 Rosendorff C et al. Treatment of hypertension in patients with coronary artery disease: A scientific statement from the American Heart Association, American College of Cardiology, and American Society of Hypertension. J Am Coll Cardiol 2015 May 12; 65:1998 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25840655
- ↑ 37.0 37.1 37.2 Edelmann F et al. Tolerability and feasibility of beta-blocker titration in HFpEF versus HFrEF: Insights from the CIBIS-ELD trial. JACC Heart Fail 2015 Dec 6 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26682793 <Internet> http://www.sciencedirect.com/science/article/pii/S2213177915006976
- ↑ 38.0 38.1 Kitzman DW et al. Effect of caloric restriction or aerobic exercise training on peak oxygen consumption and quality of life in obese older patients with heart failure with preserved ejection fraction: A randomized clinical trial. JAMA 2016 Jan 5; 315:36. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26746456
Wenger NK. Lifestyle interventions to improve exercise tolerance in obese older patients with heart failure and preserved ejection fraction. JAMA. 2016 Jan 5;315(1):31-3 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26746454 - ↑ Steinberg BA, Zhao X, Heidenreich PA et al Trends in patients hospitalized with heart failure and preserved left ventricular ejection fraction: prevalence, therapies, and outcomes. Circulation. 2012 Jul 3;126(1):65-75. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22615345 Free Article
- ↑ 40.0 40.1 40.2 40.3 Redfield MM Heart Failure with Preserved Ejection Fraction. N Engl J Med 2016; 375:1868-1877. November 10, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27959663 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMcp1511175
- ↑ 41.0 41.1 41.2 41.3 41.4 Yamamoto K. Pharmacological Treatment of Heart Failure with Preserved Ejection Fraction. Yonago Acta Med. 2017 Jun 26;60(2):71-76. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/28701888 Free PMC Article
- ↑ Oren O, Goldberg S. Heart Failure with Preserved Ejection Fraction: Diagnosis and Management. Am J Med. 2017 May;130(5):510-516. Epub 2017 Feb 3. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/28163048
- ↑ 43.0 43.1 Vaduganathan M, Patel RB, Michel A et al. Mode of Death in Heart Failure With Preserved Ejection Fraction. J Am Coll Cardiol. 2017 Feb 7;69(5):556-569. Review PMID: https://www.ncbi.nlm.nih.gov/pubmed/28153111
- ↑ 44.0 44.1 Polsinelli VB, Shah SJ. Advances in the pharmacotherapy of chronic heart failure with preserved ejection fraction: an ideal opportunity for precision medicine. Expert Opin Pharmacother. 2017 Mar;18(4):399-409. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/28129699
- ↑ Upadhya B, Pisani B, Kitzman DW Evolution of a Geriatric Syndrome: Pathophysiology and Treatment of Heart Failure With Preserved Ejection Fraction. J Am Geriatr Soc. 2017 Nov;65(11):2431-2440 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29124734
- ↑ 46.0 46.1 46.2 Zheng SL, Chan FT, Nabeebaccus AA et al. Drug treatment effects on outcomes in heart failure with preserved ejection fraction: A systematic review and meta- analysis. Heart 2017 Aug 5; pii: heartjnl-2017-311652 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28780577 Free Article <Internet> http://heart.bmj.com/content/early/2017/08/03/heartjnl-2017-311652
Van Spall HGC. Review: In HF with preserved EF, beta-blockers reduced mortality; drug treatment overall did not. Ann Intern Med 2017 Dec 19; 167:JC68 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29255858 <Internet> http://annals.org/aim/article-abstract/2666325/review-hf-preserved-ef-blockers-reduced-mortality-drug-treatment-overall - ↑ 47.0 47.1 Tsimploulis A, Lam PH, Arundel C et al Systolic Blood Pressure and Outcomes in Patients With Heart Failure With Preserved Ejection Fraction. JAMA Cardiol. Published online Feb 14, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29450487 https://jamanetwork.com/journals/jamacardiology/article-abstract/2672572
- ↑ 48.0 48.1 Vanderpool RR, Saul M, Nouraie M, Gladwin MT, Simon MA. Association Between Hemodynamic Markers of Pulmonary Hypertension and Outcomes in Heart Failure With Preserved Ejection Fraction. JAMA Cardiol. Published online March 14, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29541759 https://jamanetwork.com/journals/jamacardiology/fullarticle/2674721
- ↑ Reddy YNV, Carter RE, Obokata M et al. A simple, evidence-based approach to help guide diagnosis of heart failure with preserved ejection fraction. Circulation 2018 Aug 28; 138:861 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29792299 https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.034646
- ↑ 50.0 50.1 50.2 Borlaug BA, Anstrom KJ, Lewis GD et al. Effect of inorganic nitrite vs placebo on exercise capacity among patients with heart failure with preserved ejection fraction: The INDIE-HFpEF randomized clinical trial. JAMA 2018 Nov 6; 320:1764. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30398602 https://jamanetwork.com/journals/jama/article-abstract/2712543
- ↑ 51.0 51.1 Merrill M, Sweitzer NK, Lindenfeld J, Kao DP. Sex differences in outcomes and responses to spironolactone in heart failure with preserved ejection fraction: A secondary analysis of TOPCAT trial. JACC Heart Fail 2019 Mar; 7:228-238 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30819379 https://www.sciencedirect.com/science/article/pii/S2213177919300095
- ↑ 52.0 52.1 Balmforth C, Simpson J, Shen L et al. Outcomes and effect of treatment according to etiology in HFrEF: An analysis of PARADIGM-HF. JACC Heart Fail 2019 Jun; 7:457. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31078482 Free full text https://www.sciencedirect.com/science/article/pii/S2213177919301702
Udelson JE. Is heart failure etiology destiny? Outcome and therapeutic implications. JACC Heart Fail 2019 Jun; 7:466. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31078474 https://www.sciencedirect.com/science/article/pii/S2213177919302367 - ↑ 53.0 53.1 Beggs SAS, Rorth R, Gardner RS, McMurray JJV. Anticoagulation therapy in heart failure and sinus rhythm: A systematic review and meta-analysis. Heart 2019 Sep; 105:1325. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30962190 https://heart.bmj.com/content/105/17/1325
- ↑ 54.0 54.1 Lou N A Small Step for Olive Oil as HFpEF Treatment - Small CPET improvements suggested by preliminary diet study. MedPage Today October 4, 2020 https://www.medpagetoday.com/meetingcoverage/hfsa/88946
Billingsley H, et al Dietary supplementation of extra virgin olive oil in patients w with heart failure with preserved ejection fraction is associated with increases in cardiorespiratory fitness Heart Failure Society of Amertica (HFSA) 2020 - ↑ Armstrong PW et al. Effect of vericiguat vs placebo on quality of life in patients with heart failure and preserved ejection fraction: The VITALITY-HFpEF randomized clinical trial. JAMA 2020 Oct 20; 324:1512. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33079152 https://jamanetwork.com/journals/jama/article-abstract/2771900
Udelson JE et al. Effect of praliciguat on peak rate of oxygen consumption in patients with heart failure with preserved ejection fraction: The CAPACITY HFpEF randomized clinical trial. JAMA 2020 Oct 20; 324:1522. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33079154 https://jamanetwork.com/journals/jama/article-abstract/2771902 - ↑ 56.0 56.1 56.2 Mueller S, Winzer EB, Duvinage A et al Effect of High-Intensity Interval Training, Moderate Continuous Training, or Guideline-Based Physical Activity Advice on Peak Oxygen Consumption in Patients With Heart Failure With Preserved Ejection FractionA Randomized Clinical Trial. JAMA. 2021;325(6):542-551. Feb 9 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33560320 https://jamanetwork.com/journals/jama/fullarticle/2776199
- ↑ 57.0 57.1 57.2 Faselis C, Lam PH, Zile MR et al. Systolic blood pressure and outcomes in older patients with HFpEF and hypertension. Am J Med 2021 Apr 1; 134:e252. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33010225 https://www.amjmed.com/article/S0002-9343(20)30812-3/fulltext
- ↑ 58.0 58.1 Zhou H et al beta-blocker use and risk of mortality in heart failure patients initiating maintenance dialysis. Am J Kidney Dis 2021 May; 77:704 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33010357 https://www.ajkd.org/article/S0272-6386(20)31001-5/fulltext
- ↑ 59.0 59.1 59.2 Ferreira JP, Rossello X, Pocock SJ et al. Spironolactone dose in heart failure with preserved ejection fraction: findings from TOPCAT. Eur J Heart Fail. 2020;22(9):1615-1624 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32452128 https://onlinelibrary.wiley.com/doi/10.1002/ejhf.1909
Kalogeropoulos AP, Thankachen J, Butler J et al. Diuretic and renal effects of spironolactone and heart failure hospitalizations: a TOPCAT Americas analysis. Eur J Heart Fail. 2020;22(9):1600-1610 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32469156 https://onlinelibrary.wiley.com/doi/10.1002/ejhf.1917 - ↑ Heidenreich PA et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure. J Am Coll Cardiol 2022 Apr 1; [e-pub] PMID: https://www.ncbi.nlm.nih.gov/pubmed/35363499 Review. https://www.sciencedirect.com/science/article/abs/pii/S0735109721083959
- ↑ 61.0 61.1 Li J et al. Salt restriction and risk of adverse outcomes in heart failure with preserved ejection fraction. Heart 2022 Jul 18; [e-pub] PMID: https://www.ncbi.nlm.nih.gov/pubmed/35851318 https://heart.bmj.com/content/early/2022/06/07/heartjnl-2022-321167
- ↑ 62.0 62.1 Anker SD, Butler J, Filippatos G et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med 2021. Oct 14;385(16):1451-1461. Aug 27; [e-pub] PMID: https://www.ncbi.nlm.nih.gov/pubmed/34449189 https://www.nejm.org/doi/10.1056/NEJMoa2107038
Butler J, Filippatos G, Siddiqi TJ et al Empagliflozin, health status, and quality of life in patients with heart failure and preserved ejection fraction: The EMPEROR-Preserved Trial. Circulation 2021 Nov 15; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34779658 Free article https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.057812
Solomon SD et al. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med 2022 Aug 27; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36027570 https://www.nejm.org/doi/10.1056/NEJMoa2206286 - ↑ 63.0 63.1 Reddy YNV et al. Diagnosis of heart failure with preserved ejection fraction among patients with unexplained dyspnea. JAMA Cardiol 2022 Sep; 7:891. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35830183 PMCID: PMC9280610 (available on 2023-07-13) https://jamanetwork.com/journals/jamacardiology/fullarticle/2793877
- ↑ 64.0 64.1 Andersen MJ, Borlaug BA Heart failure with preserved ejection fraction: current understandings and challenges. Curr Cardiol Rep. 2014 Jul;16(7):501. PMID: https://www.ncbi.nlm.nih.gov/pubmed/24893938
- ↑ Redfield MM, Borlaug BA Heart Failure With Preserved Ejection Fraction. A Review. JAMA. 2023;329(10):827-838 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36917048 https://jamanetwork.com/journals/jama/fullarticle/2802310
- ↑ 66.0 66.1 66.2 Kittleson MM et al. 2023 ACC expert consensus decision pathway on management of heart failure with preserved ejection fraction: A report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 2023 May; 81:1835. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37137593 https://www.sciencedirect.com/science/article/pii/S0735109723050982
- ↑ 67.0 67.1 Vaduganathan M, Mentz RJ, Claggett BL et al Sacubitril/valsartan in heart failure with mildly reduced or preserved ejection fraction: a pre-specified participant-level pooled analysis of PARAGLIDE-HF and PARAGON-HF. Eur Heart J. 2023 Aug 14;44(31):2982-2993. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37210743 PMCID: PMC10424880 Free PMC article. Clinical Trial.
- ↑ 68.0 68.1 68.2 NEJM Knowledge+
- ↑ 69.0 69.1 Butler J, Shah SJ, Petrie MC et al Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials. Lancet. 2024 Apr 4:S0140-6736(24)00469-0 PMID: https://www.ncbi.nlm.nih.gov/pubmed/38599221
- ↑ 70.0 70.1 Gao M, Bhatia K, Kapoor A et al SGLT2 Inhibitors, Functional Capacity, and Quality of Life in Patients With Heart Failure: A Systematic Review and Meta-Analysis. JAMA Netw Open. 2024 Apr 1;7(4):e245135. PMID: https://www.ncbi.nlm.nih.gov/pubmed/38573633 Free article. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2817144
- ↑ 71.0 71.1 71.2 Carland C, Zhao L, Salman O et al Urinary Proteomics and Outcomes in Heart Failure With Preserved Ejection Fraction. J Am Heart Assoc. 2024 Apr 19:e033410. PMID: https://www.ncbi.nlm.nih.gov/pubmed/38639358 Free article. https://www.ahajournals.org/doi/10.1161/JAHA.123.033410
- ↑ 72.0 72.1 72.2 Di Palo, Feder S, Baggenstos YT et al Palliative Pharmacotherapy for Cardiovascular Disease: A Scientific Statement From the American Heart Association. Circ Cardiovasc Qual Outcomes. 2024 Jul 1:e000131 PMID: https://www.ncbi.nlm.nih.gov/pubmed/38946532 Free article. Review. https://www.ahajournals.org/doi/epdf/10.1161/HCQ.0000000000000131