Goals of treatment of chronic CHF are to:
Alleviate symptoms
Delay progression
Reduce mortality.
General principles of therapy
In newly diagnosed patients with CHF, congestion and volume overload should be promptly treated with diuretics, which may be given intravenously in the initial phase. Loop diuretics used for the treatment of heart failure and congestion include furosemide, bumetanide, and torsemide.
In patients with low left ventricular ejection fraction (LVEF), in addition to diuretics, ACE inhibitors, beta-blockers, and aldosterone antagonists (e.g., spironolactone, eplerenone) should be added.
In unstable patients, beta-blockers should be initiated only after stabilization, optimization of volume status and discontinuation of inotropes. Beta-blockers should be initiated at a low dose.
In patients with CHF and reduced LVEF who are hospitalized with exacerbation of heart failure, unless there is evidence of low cardiac output or hemodynamic instability or contraindication, both ACE-inhibitors and beta-blockers should be continued.
Lifestyle changes
The success of pharmacologic therapy is strongly related to, and greatly enhanced by, encouraging the patient and his/her family to participate in various complementary nonpharmacologic management strategies. These mainly include lifestyle changes, dietary and nutritional modifications, exercise training,[93]Flynn KE, Piña IL, Whellan DJ, et al. Effects of exercise training on health status in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA. 2009 Apr 8;301(14):1451-9.
https://jamanetwork.com/journals/jama/fullarticle/183709
http://www.ncbi.nlm.nih.gov/pubmed/19351942?tool=bestpractice.com
[94]O'Connor CM, Whellan DJ, Lee KL, et al. Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA. 2009 Apr 8;301(14):1439-50.
https://jamanetwork.com/journals/jama/fullarticle/183708
http://www.ncbi.nlm.nih.gov/pubmed/19351941?tool=bestpractice.com
[95]Smart N. Exercise training for heart failure patients with and without systolic dysfunction: an evidence-based analysis of how patients benefit. Cardiol Res Pract. 2010 Sep 30;2011:837238.
https://www.hindawi.com/journals/crp/2011/837238/
http://www.ncbi.nlm.nih.gov/pubmed/20953365?tool=bestpractice.com
and health maintenance.
Initial drug treatments
Diuretics:
All patients with symptoms and signs of congestion should receive diuretics, irrespective of the LVEF. In patients with reduced LVEF, diuretics should always be used in combination with an ACE inhibitor (or angiotensin-II receptor antagonist), a beta-blocker, and an aldosterone antagonist. Loop diuretics used for the treatment of heart failure and congestion include furosemide, bumetanide, and torsemide. The most commonly used agent appears to be furosemide, but some patients may respond more favorably to another loop diuretic. In resistant cases, loop diuretics should be combined with a thiazide diuretic (e.g., chlorothiazide, hydrochlorothiazide) or a thiazide-like diuretic (e.g., metolazone, indapamide).
Loop diuretics and thiazide diuretics differ in their pharmacologic actions. Loop diuretics increase excretion of up to 20% to 25% of the filtered load of sodium, enhance free-water clearance, and maintain their efficacy unless renal function is severely impaired. In contrast, thiazide diuretics increase the fractional excretion of sodium to only 5% to 10% of the filtered load, tend to decrease free-water clearance, and lose their effectiveness in patients with impaired renal function (i.e., creatinine clearance less than 40 mL/minute). Consequently, loop diuretics have emerged as the preferred diuretic for use in most patients with heart failure; however, thiazide diuretics may be preferred in patients with hypertension, heart failure, and mild fluid retention because they confer more persistent antihypertensive effects.
Careful monitoring of renal function and electrolytes is essential. The minimum dose of diuretic should be used to relieve congestion, keep the patient asymptomatic, and maintain a dry weight.
ACE inhibitors or beta-blockers:
ACE inhibitors
ACE inhibitors or beta-blockers may be used as first-line treatment. Both are equally important in terms of survival benefit. It has not been shown that starting the ACE inhibitor is better than starting the beta-blocker, but in practice most physicians start an ACE inhibitor first and then add a beta-blocker; the origin of this practice is historical, as the benefits of ACE inhibitors were demonstrated 10 years before those of beta-blockers. Also, most large-scale studies of beta-blockers were conducted using ACE-inhibitor therapy as comparator or standard. If a patient cannot tolerate target doses of both an ACE inhibitor and a beta-blocker when these drugs are co-administered, it is preferable to co-administer lower doses of both drugs than to reach the target dose in one class and not be able to initiate the other.
ACE inhibitors have been shown to decrease the morbidity and mortality associated with heart failure,[2]Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239.
http://www.onlinejacc.org/content/62/16/e147
http://www.ncbi.nlm.nih.gov/pubmed/23747642?tool=bestpractice.com
[92]National Institute for Health and Care Excellence. Chronic heart failure in adults: diagnosis and management. Sep 2018 [internet publication].
https://www.nice.org.uk/guidance/ng106
[96]Al-Mohammad A, Mant J, Laramee P, et al; Chronic Heart Failure Guideline Development Group. Diagnosis and management of adults with chronic heart failure: summary of updated NICE guidance. BMJ. 2010 Aug 25;341:c4130.
http://www.ncbi.nlm.nih.gov/pubmed/20739363?tool=bestpractice.com
and should be given to all patients with left ventricular (LV) dysfunction, symptomatic or otherwise, unless there is a contraindication or prior intolerance to therapy.
Beta-blockers
Beta-blockers have also been shown to decrease the morbidity and mortality associated with heart failure.[2]Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239.
http://www.onlinejacc.org/content/62/16/e147
http://www.ncbi.nlm.nih.gov/pubmed/23747642?tool=bestpractice.com
[92]National Institute for Health and Care Excellence. Chronic heart failure in adults: diagnosis and management. Sep 2018 [internet publication].
https://www.nice.org.uk/guidance/ng106
[96]Al-Mohammad A, Mant J, Laramee P, et al; Chronic Heart Failure Guideline Development Group. Diagnosis and management of adults with chronic heart failure: summary of updated NICE guidance. BMJ. 2010 Aug 25;341:c4130.
http://www.ncbi.nlm.nih.gov/pubmed/20739363?tool=bestpractice.com
They are initiated at low doses and titrated to target dosages.[2]Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239.
http://www.onlinejacc.org/content/62/16/e147
http://www.ncbi.nlm.nih.gov/pubmed/23747642?tool=bestpractice.com
[97]McAlister FA, Wiebe N, Ezekowitz JA, et al. Meta-analysis: beta-blocker dose, heart rate reduction, and death in patients with heart failure. Ann Intern Med. 2009 Jun 2;150(11):784-94.
http://www.ncbi.nlm.nih.gov/pubmed/19487713?tool=bestpractice.com
[98]Flannery G, Gehrig-Mills R, Billah B, et al. Analysis of randomized controlled trials on the effect of magnitude of heart rate reduction on clinical outcomes in patients with systolic chronic heart failure receiving beta-blockers. Am J Cardiol. 2008 Mar 15;101(6):865-9.
http://www.ncbi.nlm.nih.gov/pubmed/18328855?tool=bestpractice.com
[99]Fauchier L, Pierre B, de Labriolle A, et al. Comparison of the beneficial effect of beta-blockers on mortality in patients with ischaemic or non-ischaemic systolic heart failure: a meta-analysis of randomised controlled trials. Eur J Heart Fail. 2007 Nov;9(11):1136-9.
https://onlinelibrary.wiley.com/doi/full/10.1016/j.ejheart.2007.09.003
http://www.ncbi.nlm.nih.gov/pubmed/17936068?tool=bestpractice.com
[100]Nasr IA, Bouzamondo A, Hulot JS, et al. Prevention of atrial fibrillation onset by beta-blocker treatment in heart failure: a meta-analysis. Eur Heart J. 2007 Feb;28(4):457-62.
https://academic.oup.com/eurheartj/article/28/4/457/2887588
http://www.ncbi.nlm.nih.gov/pubmed/17289748?tool=bestpractice.com
One meta-analysis found that irrespective of pretreatment heart rate, beta-blockers reduced mortality in patients with heart failure with reduced ejection fraction (HFrEF) in sinus rhythm.[101]Kotecha D, Flather MD, Altman DG, et al. Heart rate and rhythm and the benefit of beta-blockers in patients with heart failure. J Am Coll Cardiol. 2017 Jun 20;69(24):2885-96.
http://www.onlinejacc.org/content/69/24/2885
http://www.ncbi.nlm.nih.gov/pubmed/28467883?tool=bestpractice.com
Achieving a lower heart rate is associated with better prognosis for patients in sinus rhythm but not those with atrial fibrillation. Mortality was lower for patients in sinus rhythm randomized to beta-blockers (hazard ratio: 0.73 vs. placebo; 95% confidence interval [CI] 0.67 to 0.79; P <0.001), regardless of baseline heart rate (interaction P = 0.35). Beta-blockers had no effect on mortality in patients with atrial fibrillation (hazard ratio: 0.96; 95% CI 0.81 to 1.12; P = 0.58) at any heart rate (interaction P = 0.48).[101]Kotecha D, Flather MD, Altman DG, et al. Heart rate and rhythm and the benefit of beta-blockers in patients with heart failure. J Am Coll Cardiol. 2017 Jun 20;69(24):2885-96.
http://www.onlinejacc.org/content/69/24/2885
http://www.ncbi.nlm.nih.gov/pubmed/28467883?tool=bestpractice.com
However, this was a retrospective analysis and authors commented that background therapy, including devices, may have changed since these trials were conducted and that the heart rate was not measured in a standardized fashion across the trials. In a randomized trial of patients with atrial fibrillation and HFrEF, during a median follow-up of 37 months, beta-blockers were associated with significantly lower all-cause mortality (hazard ratio: 0.721; 95% CI 0.549 to 0.945; P = 0.0180) but not hospitalization (hazard ratio: 0.886; 95% CI 0.715 to 1.100; P = 0.2232).[102]Cadrin-Tourigny J, Shohoudi A, Roy D, et al. Decreased mortality with beta-blockers in patients with heart failure and coexisting atrial fibrillation: an AF-CHF substudy. JACC Heart Fail. 2017 Feb;5(2):99-106.
http://heartfailure.onlinejacc.org/content/5/2/99
http://www.ncbi.nlm.nih.gov/pubmed/28089316?tool=bestpractice.com
The result of this study supports the evidence-based recommendations for beta-blockers in patients with HFrEF, whether or not they have associated atrial fibrillation.
Although side effects can include bradycardia, worsening of reactive airway disease, and worsening heart failure, these can often be avoided by careful patient selection, dose titration,
[
]
How does nurse-led titration of heart failure medication compare with usual care for heart failure with reduced ejection fraction?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.1391/fullShow me the answer and close monitoring. Clinical improvement may be delayed and may take 2 to 3 months to become apparent. However, long-term treatment with beta-blockers can lessen the symptoms of heart failure and improve clinical status
Angiotensin-II receptor antagonists:
Angiotensin-II receptor antagonists are considered a reasonable alternative to ACE inhibitors in patients with preserved or decreased LVEF who are intolerant of ACE inhibitors because of cough or angioedema.[2]Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239.
http://www.onlinejacc.org/content/62/16/e147
http://www.ncbi.nlm.nih.gov/pubmed/23747642?tool=bestpractice.com
[103]Heran BS, Musini VM, Bassett K, et al. Angiotensin receptor blockers for heart failure. Cochrane Database Syst Rev. 2012 Apr 18;(4):CD003040.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003040.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/22513909?tool=bestpractice.com
Experience with these drugs in controlled clinical trials of patients with heart failure is considerably less than that with ACE inhibitors. Nevertheless, valsartan and candesartan have demonstrated benefit by reducing hospitalizations and mortality.[2]Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239.
http://www.onlinejacc.org/content/62/16/e147
http://www.ncbi.nlm.nih.gov/pubmed/23747642?tool=bestpractice.com
[104]Lee VC, Rhew DC, Dylan M, et al. Meta-analysis: angiotensin-receptor blockers in chronic heart failure and high-risk acute myocardial infarction. Ann Intern Med. 2004 Nov 2;141(9):693-704. [Erratum in: Ann Intern Med. 2005 Mar 1;42(5):391.]
http://www.ncbi.nlm.nih.gov/pubmed/15520426?tool=bestpractice.com
In patients with evidence of left ventricular dysfunction early after myocardial infarction, angiotensin-II receptor antagonists may be no more effective than ACE inhibitors and may be no better tolerated. The combination of an ACE inhibitor and an angiotensin-II receptor antagonist may produce more reduction of left ventricular size[105]Wong M, Staszewsky L, Latini R, et al. Severity of left ventricular remodeling defines outcomes and response to therapy in heart failure: Valsartan heart failure trial (Val-HeFT) echocardiographic data. J Am Coll Cardiol. 2004 Jun 2;43(11):2022-7.
http://www.onlinejacc.org/content/43/11/2022
http://www.ncbi.nlm.nih.gov/pubmed/15172407?tool=bestpractice.com
and may reduce the need for hospitalization more than either agent alone, although whether or not combination therapy further reduces mortality remains unclear.[105]Wong M, Staszewsky L, Latini R, et al. Severity of left ventricular remodeling defines outcomes and response to therapy in heart failure: Valsartan heart failure trial (Val-HeFT) echocardiographic data. J Am Coll Cardiol. 2004 Jun 2;43(11):2022-7.
http://www.onlinejacc.org/content/43/11/2022
http://www.ncbi.nlm.nih.gov/pubmed/15172407?tool=bestpractice.com
[106]Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001 Dec 6;345(23):1667-75.
https://www.nejm.org/doi/10.1056/NEJMoa010713
http://www.ncbi.nlm.nih.gov/pubmed/11759645?tool=bestpractice.com
[107]McMurray JJ, Ostergren J, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet. 2003 Sep 6;362(9386):767-71.
http://www.ncbi.nlm.nih.gov/pubmed/13678869?tool=bestpractice.com
As an alternative to ACE inhibitors, angiotensin-II receptor antagonists should be initiated in patients early post-infarct, but caution should be used in patients in cardiogenic shock or with marginal renal output.[104]Lee VC, Rhew DC, Dylan M, et al. Meta-analysis: angiotensin-receptor blockers in chronic heart failure and high-risk acute myocardial infarction. Ann Intern Med. 2004 Nov 2;141(9):693-704. [Erratum in: Ann Intern Med. 2005 Mar 1;42(5):391.]
http://www.ncbi.nlm.nih.gov/pubmed/15520426?tool=bestpractice.com
Addition of an angiotensin-II receptor antagonist may be considered in persistently symptomatic patients with heart failure and reduced LVEF who are already being treated with an ACE inhibitor and beta-blockers and in whom an aldosterone antagonist is not indicated or tolerated.[2]Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239.
http://www.onlinejacc.org/content/62/16/e147
http://www.ncbi.nlm.nih.gov/pubmed/23747642?tool=bestpractice.com
Routine combined use of ACE inhibitors with an aldosterone antagonist and an angiotensin-II receptor antagonist is potentially harmful for patients with heart failure and is not recommended.[2]Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239.
http://www.onlinejacc.org/content/62/16/e147
http://www.ncbi.nlm.nih.gov/pubmed/23747642?tool=bestpractice.com
Combined use should be instigated by a specialist and continued only with specialist supervision. Concomitant administration of an ACE inhibitor, a beta-blocker, and an angiotensin-II receptor antagonist should be used with great caution, and perhaps initiated only in the hospital under continuous blood pressure and renal function monitoring because it may provoke life-threatening hypotension and acute renal insufficiency. The CHARM trial showed that this combination may confer added benefit with acceptable risk, but further studies are required.[108]Weir RA, McMurray JJ, Puu M, et al. Efficacy and tolerability of adding an angiotensin receptor blocker in patients with heart failure already receiving an angiotensin-converting inhibitor plus aldosterone antagonist, with or without a beta blocker. Findings from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Added trial. Eur J Heart Fail. 2008 Feb;10(2):157-63.
https://onlinelibrary.wiley.com/doi/full/10.1016/j.ejheart.2007.12.006
http://www.ncbi.nlm.nih.gov/pubmed/18242128?tool=bestpractice.com
In one study, addition of olmesartan (an angiotensin-II receptor antagonist) to patients with New York Heart Association (NYHA) class II to IV heart failure who had a history of hypertension or who had been treated with antihypertensive medications and were already on ACE inhibitor and beta-blocker therapy did not improve the clinical outcome and led to worsening of renal function.[109]Sakata Y, Shiba N, Takahashi J, et al. Clinical impacts of additive use of olmesartan in hypertensive patients with chronic heart failure: the supplemental benefit of an angiotensin receptor blocker in hypertensive patients with stable heart failure using olmesartan (SUPPORT) trial. Eur Heart J. 2015 Apr 14;36(15):915-23.
https://academic.oup.com/eurheartj/article/36/15/915/2293183
http://www.ncbi.nlm.nih.gov/pubmed/25637937?tool=bestpractice.com
In this study, subgroup analysis showed that the addition of olmesartan to a combination of an ACE inhibitor and a beta-blocker was associated with an increased incidence of primary end point, all-cause death, and renal dysfunction. The routine combined use of all three inhibitors of the renin-angiotensin system cannot be recommended at present. The European Medicines Agency's Pharmacovigilance Risk Assessment Committee has advised that combining drugs that act on the renin-angiotensin system (e.g., ACE inhibitors, angiotensin-II receptor antagonists) is not recommended, particularly in patients with diabetes-related kidney problems. Where such a combination is considered absolutely necessary, it should be carried out under strict specialist supervision with close monitoring.[110]European Medicines Agency. PRAC recommends against combined use of medicines affecting the renin-angiotensin (RAS) system. Apr 2014 [internet publication].
https://www.ema.europa.eu/documents/press-release/prac-recommends-against-combined-use-medicines-affecting-renin-angiotensin-ras-system_en.pdf
Renin inhibitors (e.g., aliskiren) should also not be combined with ACE inhibitors. In a study of patients with chronic heart failure (NYHA class II to IV, ejection fraction of 35% or less) addition of aliskiren to enalapril compared with enalapril alone led to more adverse events (hypotension and elevated creatinine) without any benefit or difference in primary outcome of death from cardiovascular causes or hospitalization for heart failure.[111]McMurray JJ, Krum H, Abraham WT, et al. Aliskiren, enalapril, or aliskiren and enalapril in heart failure. N Engl J Med. 2016 Apr 21;374(16):1521-32.
https://www.nejm.org/doi/full/10.1056/NEJMoa1514859
http://www.ncbi.nlm.nih.gov/pubmed/27043774?tool=bestpractice.com
Angiotensin-II receptor antagonist plus neprilysin inhibitor:
In HFrEF (NYHA class II to IV) and ejection fraction of 40% or less, which was later changed to an ejection fraction of 35% or less, a combination of sacubitril, a neprilysin inhibitor, and valsartan, an angiotensin-II receptor antagonist, was superior to enalapril in reducing mortality and heart failure hospitalization.[112]McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004.
https://www.nejm.org/doi/full/10.1056/NEJMoa1409077
http://www.ncbi.nlm.nih.gov/pubmed/25176015?tool=bestpractice.com
The drug combination has been approved in the US and in Europe for the treatment of heart failure. In this study the ejection fraction was 29 ± 6.1% in the sacubitril/valsartan group and 29.4 ± 6.3% in the enalapril group.[112]McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004.
https://www.nejm.org/doi/full/10.1056/NEJMoa1409077
http://www.ncbi.nlm.nih.gov/pubmed/25176015?tool=bestpractice.com
Sacubitril/valsartan has been found to improve a patient's physical and social activities compared with enalapril.[113]Chandra A, Lewis EF, Claggett BL, et al. Effects of sacubitril/valsartan on physical and social activity limitations in patients with heart failure: a secondary analysis of the PARADIGM-HF trial. JAMA Cardiol. 2018 Jun 1;3(6):498-505.
http://www.ncbi.nlm.nih.gov/pubmed/29617523?tool=bestpractice.com
Sacubitril/valsartan is recommended as a replacement for an ACE inhibitor in patients who remain symptomatic despite optimal treatment with an ACE inhibitor, a beta-blocker, and a mineralocorticoid-receptor antagonist.[1]Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Eur J Heart Fail. 2016 Aug;18(8):891-975.
https://onlinelibrary.wiley.com/doi/full/10.1002/ejhf.592
http://www.ncbi.nlm.nih.gov/pubmed/27207191?tool=bestpractice.com
It is recommended for patients who fit the profile of the study showing beneficial effects of this combination (i.e., patients in NYHA class II to IV with LVEF of 35% or <35%).[112]McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004.
https://www.nejm.org/doi/full/10.1056/NEJMoa1409077
http://www.ncbi.nlm.nih.gov/pubmed/25176015?tool=bestpractice.com
The American Heart Association/American College of Cardiology/Heart Failure Society of America guidelines recommend that, in patients with chronic NYHA class II or III who tolerate an ACE inhibitor or angiotensin-II receptor antagonist, these drugs should be replaced by an angiotensin-II receptor antagonist plus neprilysin inhibitor to further reduce morbidity and mortality.[70]Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017 Aug 8;136(6):e137-61.
https://www.ahajournals.org/doi/full/10.1161/cir.0000000000000509
http://www.ncbi.nlm.nih.gov/pubmed/28455343?tool=bestpractice.com
Concomitant administration of an angiotensin-II receptor antagonist plus a neprilysin inhibitor with an ACE inhibitor, or within 36 hours of the last dose of an ACE inhibitor, is not recommended.[70]Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017 Aug 8;136(6):e137-61.
https://www.ahajournals.org/doi/full/10.1161/cir.0000000000000509
http://www.ncbi.nlm.nih.gov/pubmed/28455343?tool=bestpractice.com
Treatment with sacubitril/valsartan reduces cardiovascular death by reducing both worsening heart failure and sudden cardiac death.[114]Desai AS, McMurray JJ, Packer M, et al. Effect of the angiotensin-receptor-neprilysin inhibitor LCZ696 compared with enalapril on mode of death in heart failure patients. Eur Heart J. 2015 Aug 7;36(30):1990-7.
https://academic.oup.com/eurheartj/article/36/30/1990/2398127
http://www.ncbi.nlm.nih.gov/pubmed/26022006?tool=bestpractice.com
Hydralazine and nitrates:
The addition of a combination of hydralazine and a nitrate is reasonable for patients with reduced LVEF who are already taking an ACE inhibitor and beta-blocker for symptomatic heart failure and who have persistent symptoms,[2]Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239.
http://www.onlinejacc.org/content/62/16/e147
http://www.ncbi.nlm.nih.gov/pubmed/23747642?tool=bestpractice.com
and has demonstrated benefit in black patients with heart failure.[115]Carson P, Ziesche S, Johnson G, et al; Vasodilator-Heart Failure Trial Study Group. Racial differences in response to therapy for heart failure: analysis of the vasodilator-heart failure trials. J Card Fail. 1999 Sep;5(3):178-87.
http://www.ncbi.nlm.nih.gov/pubmed/10496190?tool=bestpractice.com
[116]Taylor AL, Ziesche S, Yancy C, et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med. 2004 Nov 11;351(20):2049-57.
https://www.nejm.org/doi/10.1056/NEJMoa042934
http://www.ncbi.nlm.nih.gov/pubmed/15533851?tool=bestpractice.com
The combined use of hydralazine and isosorbide dinitrate may also be considered as a therapeutic option in patients who are intolerant of ACE inhibitors.[2]Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239.
http://www.onlinejacc.org/content/62/16/e147
http://www.ncbi.nlm.nih.gov/pubmed/23747642?tool=bestpractice.com
This combination may be a useful alternative in patients intolerant to both ACE inhibitors and angiotensin-II receptor antagonists.[2]Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239.
http://www.onlinejacc.org/content/62/16/e147
http://www.ncbi.nlm.nih.gov/pubmed/23747642?tool=bestpractice.com
A combination of hydralazine and isosorbide dinitrate can be useful to reduce morbidity or mortality in patients with current or prior symptomatic HFrEF who cannot be given an ACE inhibitor or angiotensin-II receptor antagonist because of drug intolerance, hypotension, or renal insufficiency, unless contraindicated.[2]Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239.
http://www.onlinejacc.org/content/62/16/e147
http://www.ncbi.nlm.nih.gov/pubmed/23747642?tool=bestpractice.com
The American College of Cardiology Foundation/American Heart Association guidelines recommend the combination of hydralazine and isosorbide dinitrate to 'reduce morbidity and mortality in patients self-described as African Americans with NYHA class III to IV HFrEF receiving optimal therapy with ACE inhibitors and beta blockers, unless contraindicated'.[2]Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239.
http://www.onlinejacc.org/content/62/16/e147
http://www.ncbi.nlm.nih.gov/pubmed/23747642?tool=bestpractice.com
Anticoagulants:
At present there is little evidence from long-term studies to recommend antiplatelet therapy or oral anticoagulation in patients with heart failure in sinus rhythm, and antiplatelet agents versus control or anticoagulation for heart failure in sinus rhythm.[117]Lip GY, Shantsila E. Anticoagulation versus placebo for heart failure in sinus rhythm. Cochrane Database Syst Rev. 2014 Mar 28;(3):CD003336.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003336.pub3/full
http://www.ncbi.nlm.nih.gov/pubmed/24683002?tool=bestpractice.com
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In people with heart failure who are in sinus rhythm, does anticoagulation improve outcomes when compared with placebo?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.417/fullShow me the answer
A study comparing warfarin and aspirin in patients with heart failure and sinus rhythm showed no significant difference in the combined outcomes of stroke, intracerebral hemorrhage, and death. Warfarin reduced ischemic stroke at the expense of an increased bleeding risk.[118]Homma S, Thompson JL, Pullicino PM, et al. Warfarin and aspirin in patients with heart failure and sinus rhythm. N Engl J Med. 2012 May 17;366(20):1859-69.
https://www.nejm.org/doi/10.1056/NEJMoa1202299
http://www.ncbi.nlm.nih.gov/pubmed/22551105?tool=bestpractice.com
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How do warfarin and aspirin compare in adults with congestive heart failure in sinus rhythm?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.1490/fullShow me the answer
Although oral anticoagulants are indicated in certain groups of patients with heart failure (e.g., patients with atrial fibrillation), the available data do not support their routine use in heart failure patients who remain in sinus rhythm.[117]Lip GY, Shantsila E. Anticoagulation versus placebo for heart failure in sinus rhythm. Cochrane Database Syst Rev. 2014 Mar 28;(3):CD003336.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003336.pub3/full
http://www.ncbi.nlm.nih.gov/pubmed/24683002?tool=bestpractice.com
Digoxin for patients with heart failure
Digoxin can be beneficial in patients with current or prior symptoms of heart failure or reduced LVEF, especially those with atrial fibrillation. When added to ACE inhibitors, beta-blockers, and diuretics, digoxin can reduce symptoms, prevent hospitalization, control rhythm, and enhance exercise tolerance.[119]Roy D, Talajic M, Nattel S, et al. Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med. 2008 Jun 19;358(25):2667-77.
https://www.nejm.org/doi/10.1056/NEJMoa0708789
http://www.ncbi.nlm.nih.gov/pubmed/18565859?tool=bestpractice.com
Digoxin reduces the composite end point of mortality or hospitalizations in ambulatory patients with chronic heart failure with NYHA class III or IV symptoms, LVEF <25%, or cardiothoracic ratio of >55% and should be considered in these patients.[120]Gheorghiade M, Patel K, Filippatos G, et al. Effect of oral digoxin in high-risk heart failure patients: a pre-specified subgroup analysis of the DIG trial. Eur J Heart Fail. 2013 May;15(5):551-9.
https://onlinelibrary.wiley.com/doi/full/10.1093/eurjhf/hft010
http://www.ncbi.nlm.nih.gov/pubmed/23355060?tool=bestpractice.com
Digoxin reduces the composite end point of mortality or hospitalizations, but does not reduce all-cause mortality.[120]Gheorghiade M, Patel K, Filippatos G, et al. Effect of oral digoxin in high-risk heart failure patients: a pre-specified subgroup analysis of the DIG trial. Eur J Heart Fail. 2013 May;15(5):551-9.
https://onlinelibrary.wiley.com/doi/full/10.1093/eurjhf/hft010
http://www.ncbi.nlm.nih.gov/pubmed/23355060?tool=bestpractice.com
Digoxin should be used cautiously with plasma level monitoring. One meta-analysis suggests that digoxin use in patients with heart failure is associated with a higher risk of all-cause mortality.[121]Vamos M, Erath JW, Hohnloser SH, et al. Digoxin-associated mortality: a systematic review and meta-analysis of the literature. Eur Heart J. 2015 Jul 21;36(28):1831-8.
https://academic.oup.com/eurheartj/article/36/28/1831/2398087
http://www.ncbi.nlm.nih.gov/pubmed/25939649?tool=bestpractice.com
One systematic review and meta-analysis of observational and controlled trial data showed that digoxin has a neutral effect on mortality in randomized trials and reduces hospital admissions.[122]Ziff OJ, Lane DA, Samra M, et al. Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data. BMJ. 2015 Aug 30;351:h4451.
https://www.bmj.com/content/351/bmj.h4451.long
http://www.ncbi.nlm.nih.gov/pubmed/26321114?tool=bestpractice.com
Aldosterone antagonists in moderate-to-severe heart failure
Aldosterone antagonists (also known as mineralocorticoid receptor antagonists) decrease the morbidity and mortality associated with symptomatic chronic heart failure.
Aldosterone antagonists (spironolactone and eplerenone) are recommended in patients with NYHA class II to IV heart failure who have LVEF of 35% or less, unless contraindicated.[2]Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239.
http://www.onlinejacc.org/content/62/16/e147
http://www.ncbi.nlm.nih.gov/pubmed/23747642?tool=bestpractice.com
They are also recommended to reduce mortality and morbidity following acute myocardial infarction in patients with LVEF of 40% or less who develop symptoms of heart failure or have a history of diabetes mellitus, unless contraindicated.[2]Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239.
http://www.onlinejacc.org/content/62/16/e147
http://www.ncbi.nlm.nih.gov/pubmed/23747642?tool=bestpractice.com
[123]Fox K, Ford I, Steg PG, et al. Ivabradine in stable coronary artery disease without clinical heart failure. N Engl J Med. 2014 Sep 18;371(12):1091-9.
https://www.nejm.org/doi/full/10.1056/NEJMoa1406430
http://www.ncbi.nlm.nih.gov/pubmed/25176136?tool=bestpractice.com
Aldosterone antagonists should be initiated after titration of standard medical therapy. Spironolactone and eplerenone can both cause hyperkalemia, and precautions should be taken to minimize the risk. In the EPHESUS trial, the addition of eplerenone to standard care did not increase the risk of hyperkalemia when potassium was regularly monitored.[124]Pitt B, Bakris G, Ruilope LM, et al. Serum potassium and clinical outcomes in the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Circulation. 2008 Oct 14;118(16):1643-50.
http://www.ncbi.nlm.nih.gov/pubmed/18824643?tool=bestpractice.com
Ivabradine
Ivabradine is approved for use in patients with heart failure and symptoms in spite of drug therapy. The Food and Drug Administration (FDA) has approved it to reduce the risk of hospitalization for worsening heart failure in patients with stable, symptomatic chronic heart failure, with LVEF ≤35%, who are in sinus rhythm with a resting heart rate ≥70 beats per minute and are either on a maximum dose of beta-blockers or have a contraindication to beta-blockers.
In a randomized, double-blind, placebo-controlled trial, addition of ivabradine to standard background therapy in patients with stable coronary artery disease without clinical heart failure (no evidence of left ventricular systolic dysfunction in the overall study population, mean ejection fraction was 56.4%) did not improve the outcome. In the subgroup analysis of this study, ivabradine was associated with an increase in the incidence of the primary end point (death from cardiovascular causes or nonfatal myocardial infarction) among patients who had angina of Canadian Cardiovascular Society class II or higher but not among patients without angina or those who had angina of class I. Ivabradine was associated with an increased incidence of bradycardia, QT prolongation, and atrial fibrillation.[123]Fox K, Ford I, Steg PG, et al. Ivabradine in stable coronary artery disease without clinical heart failure. N Engl J Med. 2014 Sep 18;371(12):1091-9.
https://www.nejm.org/doi/full/10.1056/NEJMoa1406430
http://www.ncbi.nlm.nih.gov/pubmed/25176136?tool=bestpractice.com
Vasopressin antagonists
Use of vasopressin antagonists such as tolvaptan can be considered for patients with symptomatic or severe hyponatremia (<130 mmol/L) and persistent congestion despite standard therapy, to correct hyponatremia and related symptoms.[2]Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239.
http://www.onlinejacc.org/content/62/16/e147
http://www.ncbi.nlm.nih.gov/pubmed/23747642?tool=bestpractice.com
[125]McKelvie RS, Moe GW, Ezekowitz JA, et al. The 2012 Canadian Cardiovascular Society heart failure management guidelines update: focus on acute and chronic heart failure. Can J Cardiol. 2013 Feb;29(2):168-81.
http://www.ncbi.nlm.nih.gov/pubmed/23201056?tool=bestpractice.com
Heart transplant and medical devices
Cardiac transplantation is currently the only established surgical approach, but it is available to fewer than 2500 patients in the US each year.[126]Mudge GH, Goldstein S, Addonizio LJ, et al. 24th Bethesda conference: Cardiac transplantation. Task Force 3: Recipient guidelines/prioritization. J Am Coll Cardiol. 1993 Jul;22(1):21-31.
http://www.onlinejacc.org/content/22/1/21
http://www.ncbi.nlm.nih.gov/pubmed/8509544?tool=bestpractice.com
[127]Mehra MR, Canter CE, Hannan MM, et al. The 2016 International Society for Heart Lung Transplantation listing criteria for heart transplantation: a 10-year update. J Heart Lung Transplant. 2016 Jan;35(1):1-23.
http://www.ncbi.nlm.nih.gov/pubmed/26776864?tool=bestpractice.com
[128]Mehra MR, Kobashigawa JA. Advances in heart and lung transplantation 2004: report from the 24th International Society for Heart and Lung Transplantation Annual Meeting, San Francisco, 21-24 April 2004. J Heart Lung Transplant. 2004 Aug;23(8):925-30.
http://www.ncbi.nlm.nih.gov/pubmed/15312821?tool=bestpractice.com
Current indications for cardiac transplantation focus on the identification of patients with severe functional impairment, dependence on intravenous inotropic agents, recurrent life-threatening ventricular arrhythmias, or angina that is refractory to all currently available treatments.[2]Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239.
http://www.onlinejacc.org/content/62/16/e147
http://www.ncbi.nlm.nih.gov/pubmed/23747642?tool=bestpractice.com
[127]Mehra MR, Canter CE, Hannan MM, et al. The 2016 International Society for Heart Lung Transplantation listing criteria for heart transplantation: a 10-year update. J Heart Lung Transplant. 2016 Jan;35(1):1-23.
http://www.ncbi.nlm.nih.gov/pubmed/26776864?tool=bestpractice.com
[128]Mehra MR, Kobashigawa JA. Advances in heart and lung transplantation 2004: report from the 24th International Society for Heart and Lung Transplantation Annual Meeting, San Francisco, 21-24 April 2004. J Heart Lung Transplant. 2004 Aug;23(8):925-30.
http://www.ncbi.nlm.nih.gov/pubmed/15312821?tool=bestpractice.com
[129]Miller LW. Listing criteria for cardiac transplantation: results of an American Society of Transplant Physicians-National Institutes of Health conference. Transplantation. 1998 Oct 15;66(7):947-51.
http://www.ncbi.nlm.nih.gov/pubmed/9798715?tool=bestpractice.com
Implantable defibrillators have been shown to decrease mortality in patients with heart failure, both ischemic and nonischemic. The SCD-Heft trial enrolled patients who had left ventricular dysfunction and no prior history of syncope or sustained ventricular tachycardia, and included patients with a prior myocardial infarction and no prior coronary artery disease. Use of implantable defibrillators led to a 23% relative mortality risk reduction at 5 years.[130]Bardy GH, Lee KL, Mark DB, Poole JE, et al; Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) Investigators. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med. 2005 Jan 20;352(3):225-37.
https://www.nejm.org/doi/full/10.1056/NEJMoa043399
http://www.ncbi.nlm.nih.gov/pubmed/15659722?tool=bestpractice.com
It has been estimated that one quarter to one third of patients with heart failure have left bundle-branch block: that is, manifest a QRS duration greater than 120 milliseconds (ms).[131]Jarcho JA. Biventricular pacing. N Engl J Med. 2006 Jul 20;355(3):288-94.
http://www.ncbi.nlm.nih.gov/pubmed/16855269?tool=bestpractice.com
Patients with heart failure who have left bundle-branch block, known as ventricular dyssynchrony, have a poorer prognosis than those without left bundle-branch block.[2]Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239.
http://www.onlinejacc.org/content/62/16/e147
http://www.ncbi.nlm.nih.gov/pubmed/23747642?tool=bestpractice.com
Studies have shown that, in these patients, cardiac resynchronization therapy (CRT) decreases hospitalization and, when combined with an implantable defibrillator, significantly reduces mortality.[132]Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 2004 May 20;350(21):2140-50.
https://www.nejm.org/doi/10.1056/NEJMoa032423
http://www.ncbi.nlm.nih.gov/pubmed/15152059?tool=bestpractice.com
[133]De Marco T, Wolfel E, Feldman AM, et al. Impact of cardiac resynchronization therapy on exercise performance, functional capacity, and quality of life in systolic heart failure with QRS prolongation: COMPANION trial sub-study. J Card Fail. 2008 Feb;14(1):9-18.
http://www.ncbi.nlm.nih.gov/pubmed/18226768?tool=bestpractice.com
[134]Linde C, Abraham WT, Gold MR, et al. Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms. J Am Coll Cardiol. 2008 Dec 2;52(23):1834-43.
http://www.onlinejacc.org/content/52/23/1834
http://www.ncbi.nlm.nih.gov/pubmed/19038680?tool=bestpractice.com
[135]Mark DB, Anstrom KJ, Sun JL, et al. Quality of life with defibrillator therapy or amiodarone in heart failure. N Engl J Med. 2008 Sep 4;359(10):999-1008.
https://www.nejm.org/doi/10.1056/NEJMoa0706719
http://www.ncbi.nlm.nih.gov/pubmed/18768943?tool=bestpractice.com
[136]Bertoldi EG, Polanczyk CA, Cunha V, et al. Mortality reduction of cardiac resynchronization and implantable cardioverter-defibrillator therapy in heart failure: an updated meta-analysis. Does recent evidence change the standard of care? J Card Fail. 2011 Oct;17(10):860-6.
http://www.ncbi.nlm.nih.gov/pubmed/21962425?tool=bestpractice.com
[137]Cleland JG, Freemantle N, Erdmann E, et al. Long-term mortality with cardiac resynchronization therapy in the Cardiac Resynchronization-Heart Failure (CARE-HF) trial. Eur J Heart Fail. 2012 Jun;14(6):628-34.
https://onlinelibrary.wiley.com/doi/full/10.1093/eurjhf/hfs055
http://www.ncbi.nlm.nih.gov/pubmed/22552183?tool=bestpractice.com
In patients who have conduction delay and left ventricular dysfunction, biventricular pacemakers have been shown to improve exercise tolerance and quality of life while decreasing morbidity and mortality.[132]Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 2004 May 20;350(21):2140-50.
https://www.nejm.org/doi/10.1056/NEJMoa032423
http://www.ncbi.nlm.nih.gov/pubmed/15152059?tool=bestpractice.com
[133]De Marco T, Wolfel E, Feldman AM, et al. Impact of cardiac resynchronization therapy on exercise performance, functional capacity, and quality of life in systolic heart failure with QRS prolongation: COMPANION trial sub-study. J Card Fail. 2008 Feb;14(1):9-18.
http://www.ncbi.nlm.nih.gov/pubmed/18226768?tool=bestpractice.com
[134]Linde C, Abraham WT, Gold MR, et al. Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms. J Am Coll Cardiol. 2008 Dec 2;52(23):1834-43.
http://www.onlinejacc.org/content/52/23/1834
http://www.ncbi.nlm.nih.gov/pubmed/19038680?tool=bestpractice.com
[135]Mark DB, Anstrom KJ, Sun JL, et al. Quality of life with defibrillator therapy or amiodarone in heart failure. N Engl J Med. 2008 Sep 4;359(10):999-1008.
https://www.nejm.org/doi/10.1056/NEJMoa0706719
http://www.ncbi.nlm.nih.gov/pubmed/18768943?tool=bestpractice.com
[137]Cleland JG, Freemantle N, Erdmann E, et al. Long-term mortality with cardiac resynchronization therapy in the Cardiac Resynchronization-Heart Failure (CARE-HF) trial. Eur J Heart Fail. 2012 Jun;14(6):628-34.
https://onlinelibrary.wiley.com/doi/full/10.1093/eurjhf/hfs055
http://www.ncbi.nlm.nih.gov/pubmed/22552183?tool=bestpractice.com
[138]Cazeau S, Leclercq C, Lavergne T, et al. Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med. 2001 Mar 22;344(12):873-80.
https://www.nejm.org/doi/10.1056/NEJM200103223441202
http://www.ncbi.nlm.nih.gov/pubmed/11259720?tool=bestpractice.com
[139]Nelson GS, Berger RD, Fetics BJ, et al. Left ventricular or biventricular pacing improves cardiac function at diminished energy cost in patients with dilated cardiomyopathy and left bundle-branch block. Circulation. 2000 Dec 19;102(25):3053-9.
http://www.ncbi.nlm.nih.gov/pubmed/11120694?tool=bestpractice.com
[140]Abraham WT, Fisher WG, Smith AL, et al. Cardiac resynchronization in chronic heart failure. N Engl J Med. 2002 Jun 13;346(24):1845-53.
https://www.nejm.org/doi/10.1056/NEJMoa013168
http://www.ncbi.nlm.nih.gov/pubmed/12063368?tool=bestpractice.com
The CARE-HF study randomized patients with a widened QRS, LVEF of 35% or less, and persistent moderate or severe symptoms of heart failure despite pharmacologic therapy, to implantation of a CRT device or not.[141]Cleland JG, Daubert JC, Erdmann E, et al. The CARE-HF study (CArdiac REsynchronisation in Heart Failure study): rationale, design and end-points. Eur J Heart Fail. 2001 Aug;3(4):481-9.
https://onlinelibrary.wiley.com/doi/full/10.1016/S1388-9842%2801%2900176-3
http://www.ncbi.nlm.nih.gov/pubmed/11511435?tool=bestpractice.com
The main study observed substantial benefits on morbidity and mortality that persisted or increased with longer follow-up.[142]Cleland JG, Daubert JC, Erdmann E, et al. Longer-term effects of cardiac resynchronization therapy on mortality in heart failure [the CArdiac REsynchronization-Heart Failure (CARE-HF) trial extension phase]. Eur Heart J. 2006 Aug;27(16):1928-32.
https://academic.oup.com/eurheartj/article/27/16/1928/2887143
http://www.ncbi.nlm.nih.gov/pubmed/16782715?tool=bestpractice.com
[143]Calvert MJ, Freemantle N, Cleland JG. The impact of chronic heart failure on health-related quality of life data acquired in the baseline phase of the CARE-HF study. Eur J Heart Fail. 2005 Mar 2;7(2):243-51.
https://onlinelibrary.wiley.com/doi/full/10.1016/j.ejheart.2005.01.012
http://www.ncbi.nlm.nih.gov/pubmed/15701474?tool=bestpractice.com
[144]Calvert MJ, Freemantle N, Yao G, et al. Cost-effectiveness of cardiac resynchronization therapy: results from the CARE-HF trial. Eur Heart J. 2005 Dec;26(24):2681-8.
https://academic.oup.com/eurheartj/article/26/24/2681/2888051
http://www.ncbi.nlm.nih.gov/pubmed/16284203?tool=bestpractice.com
[145]Ellenbogen KA, Wood MA, Klein HU. Why should we care about CARE-HF? J Am Coll Cardiol. 2005 Dec 20;46(12):2199-203.
http://www.onlinejacc.org/content/46/12/2199
http://www.ncbi.nlm.nih.gov/pubmed/16360046?tool=bestpractice.com
[146]Hoppe UC, Casares JM, Eiskjaer H, et al. Effect of cardiac resynchronization on the incidence of atrial fibrillation in patients with severe heart failure. Circulation. 2006 Jul 4;114(1):18-25.
http://www.ncbi.nlm.nih.gov/pubmed/16801461?tool=bestpractice.com
[147]Cleland JG, Daubert JC, Erdmann E, et al. Baseline characteristics of patients recruited into the CARE-HF study. Eur J Heart Fail. 2005 Mar 2;7(2):205-14.
https://onlinelibrary.wiley.com/doi/abs/10.1016/j.ejheart.2005.01.010
http://www.ncbi.nlm.nih.gov/pubmed/15701468?tool=bestpractice.com
[148]Cleland JG, Daubert JC, Erdmann E, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005 Apr 14;352(15):1539-49.
https://www.nejm.org/doi/10.1056/NEJMoa050496
http://www.ncbi.nlm.nih.gov/pubmed/15753115?tool=bestpractice.com
[149]Cleland JG, Calvert MJ, Verboven Y, et al. Effects of cardiac resynchronization therapy on long-term quality of life: an analysis from the CArdiac Resynchronisation-Heart Failure (CARE-HF) study. Am Heart J. 2009 Mar;157(3):457-66.
http://www.ncbi.nlm.nih.gov/pubmed/19249415?tool=bestpractice.com
[150]Ghio S, Freemantle N, Scelsi L, et al. Long-term left ventricular reverse remodelling with cardiac resynchronization therapy: results from the CARE-HF trial. Eur J Heart Fail. 2009 May;11(5):480-8.
https://onlinelibrary.wiley.com/doi/full/10.1093/eurjhf/hfp034
http://www.ncbi.nlm.nih.gov/pubmed/19287017?tool=bestpractice.com
[151]Cleland J, Freemantle N, Ghio S, et al. Predicting the long-term effects of cardiac resynchronization therapy on mortality from baseline variables and the early response a report from the CARE-HF (Cardiac Resynchronization in Heart Failure) Trial. J Am Coll Cardiol. 2008 Aug 5;52(6):438-45.
http://www.onlinejacc.org/content/52/6/438
http://www.ncbi.nlm.nih.gov/pubmed/18672164?tool=bestpractice.com
[152]Lindenfeld J, Feldman AM, Saxon L, et al. Effects of cardiac resynchronization therapy with or without a defibrillator on survival and hospitalizations in patients with New York Heart Association class IV heart failure. Circulation. 2007 Jan 16;115(2):204-12.
http://www.ncbi.nlm.nih.gov/pubmed/17190867?tool=bestpractice.com
Reduction in mortality was due to fewer deaths from heart failure and from reduced sudden death.[142]Cleland JG, Daubert JC, Erdmann E, et al. Longer-term effects of cardiac resynchronization therapy on mortality in heart failure [the CArdiac REsynchronization-Heart Failure (CARE-HF) trial extension phase]. Eur Heart J. 2006 Aug;27(16):1928-32.
https://academic.oup.com/eurheartj/article/27/16/1928/2887143
http://www.ncbi.nlm.nih.gov/pubmed/16782715?tool=bestpractice.com
The FDA approved the use of CRT devices for patients in NYHA class II heart failure, an LVEF <30%, left bundle-branch block, and QRS width >130 ms. Long-term data from the REVERSE study suggest that improvements in left ventricular function and remodeling can be sustained for over 5 years.[153]Daubert C, Gold MR, Abraham WT, et al. Prevention of disease progression by cardiac resynchronization therapy in patients with asymptomatic or mildly symptomatic left ventricular dysfunction. J Am Coll Cardiol. 2009 Nov 10;54(20):1837-46.
http://www.onlinejacc.org/content/54/20/1837
http://www.ncbi.nlm.nih.gov/pubmed/19800193?tool=bestpractice.com
[154]Linde C, Gold MR, Abraham WT, et al. REVERSE study: CRT produces long-term improvements in disease progression in mildly symptomatic heart failure patients. Five-year results from the REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction study. Paper presented at: European Society of Cardiology Congress 2012. 27 August 2012. Munich, Germany.
According to the American College of Cardiology Foundation/American Heart Association guidelines, the recommendations for the use of CRT devices in heart failure are as follows.[2]Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239.
http://www.onlinejacc.org/content/62/16/e147
http://www.ncbi.nlm.nih.gov/pubmed/23747642?tool=bestpractice.com
CRT is indicated in patients who have LVEF of 35% or less; sinus rhythm; left bundle-branch block (LBBB) with a QRS duration of 150 ms or greater; NYHA class II, III, or ambulatory IV symptoms on guideline-directed medical therapy.
CRT can be useful in patients who have LVEF of 35% or less; sinus rhythm; a non-LBBB with a QRS duration of 150 ms or greater; NYHA class III/ambulatory IV symptoms on guideline-directed medical therapy.
CRT can be useful in patients who have LVEF of 35% or less; sinus rhythm; LBBB with a QRS duration of 120 to 149 ms; NYHA class II, III, or ambulatory IV symptoms on guideline-directed medical therapy.
CRT can be useful in patients with atrial fibrillation and LVEF of 35% or less on guideline-directed medical therapy if (a) the patient requires pacing or otherwise meets the CRT criteria; and (b) atrioventricular nodal ablation or pharmacological rate control will allow near 100% ventricular pacing with CRT.
CRT can be useful for patients on guideline-directed medical therapy who have LVEF of 35% or less and are undergoing device implantation with anticipated requirement for significant (>40%) ventricular pacing.
American Heart Association guidance outlines the indication and evidence behind the use of mechanical circulatory support in patients with heart failure.[155]Peura JL, Colvin-Adams M, Francis GS, et al. Recommendations for the use of mechanical circulatory support: device strategies and patient selection. A scientific statement from the American Heart Association. Circulation. 2012 Nov 27;126(22):2648-67.
https://www.ahajournals.org/doi/full/10.1161/cir.0b013e3182769a54
http://www.ncbi.nlm.nih.gov/pubmed/23109468?tool=bestpractice.com
Mechanical circulatory support, which includes ventricular assist devices, is beneficial in carefully selected patients with end-stage D heart failure in whom definite management ( e.g., cardiac transplantation) or cardiac recovery is anticipated.[2]Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239.
http://www.onlinejacc.org/content/62/16/e147
http://www.ncbi.nlm.nih.gov/pubmed/23747642?tool=bestpractice.com