Chronic heart failure resident survival guide
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mahmoud Sakr, M.D. [2] Ayokunle Olubaniyi, M.B,B.S [3]
Definitions
Definition | |
---|---|
Heart failure | This is a complex syndrome whereby there is inadequate output of the heart to meet the metabolic demands of the body. Heart failure is a clinical syndrome characterized by symptoms of dyspnea, edema and fatigue and signs such as rales on physical examination. |
Heart failure with preserved ejection fraction (HFpEF) | This is otherwise called diastolic HF. It is characterized with an ejection fraction ≥ 50%. |
Heart failure with reduced ejection fraction (HFrEF) | This is also called systolic HF. It is characterized with an ejection fraction of ≤ 40%. |
Advanced heart failure | |
Guideline-directed medical therapy (GDMT) | This is a term which represents the optimal medical therapy in the management of heart failure as defined by ACCF/AHA. These are primarily the class 1 recommendations. It involves the use of ACE inhibitors or (ARBs), beta blockers, aldosterone antagonists, and hydralazine/nitrate medications. |
Goals of Therapy
Goals | Therapeutic intervention |
---|---|
To alleviate symptoms | Diuretics |
To reduce mortality | ACE inhibitors[1][2], ARBs, beta blockers[3], aldosterone antagonists[4], hydralazine plus isosorbide dinitrate[5], Omega-3 fatty acid[6][7], CRT[8], ICD[9] |
To reduce hospitalization | Digoxin[10], ARBs (in HFpEF)[11] |
Treat underlying cardiovascular disease |
Classifciation
ACCF/AHA Stages of Heart Failure
Stage of Heart Failure | Description |
---|---|
A | At high risk for HF but without structural heart disease or symptoms of HF. |
B | Structural heart disease but without signs or symptoms of HF. |
C | Structural heart disease with prior or current symptoms of HF. |
D | Refractory HF requiring specialized interventions. |
ACCF - American College of Cardiology Foundation; AHA - American Heart Association.
New York Heart Association (NYHA)
Stage of Heart Failure | Description |
---|---|
I | No limitation of physical activity. Ordinary physical activity does not cause symptoms of HF. |
II | Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in symptoms of HF. |
III | Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes symptoms of HF. |
IV | Unable to carry on any physical activity without symptoms of HF, or symptoms of HF at rest. |
Causes
Life Threatening Causes
Acute decompensated heart failure is a life-threatening condition and must be treated as such irrespective of the causes. Life-threatening conditions can result in death or permanent disability within 24 hours if left untreated.
- Accelerated hypertension
- Acute kidney injury
- Acute myocardial ischemia
- Acute or progressive valvular disease (e.g. acute mitral regurgitation)
- Acute or subacute valve disease endocarditis
- Aortic dissection
- Cardiac arrhythmias, especially ventricular arrhythmias
- Cardiotoxic agents (e.g. alcohol, cocaine, and certain chemotherapy drugs)
- Diabetic emergencies (e.g. ketoacidosis)
- Myopericarditis
- Pulmonary embolus
- Severe anemia (e.g. acute hemolysis or blood loss)
- Systemic Inflammatory response syndrome
- Thyrotoxicosis
Common Causes
- Noncompliance with dietary restrictions (e.g., sodium and fluid restriction)
- Electrolyte imbalances
- Cardiotoxic drugs (e.g. NSAIDs, thiazolidinedione, and certain chemotherapy drugs)
- Uncontrolled hypertension
- Anemia
- Progressive valvular disease (e.g. mitral regurgitation)
- Uncontrolled arrhythmias
- Excessive alcohol or illicit drug use (e.g. cocaine)
- Myocardial ischemia or infarction
- Pulmonary embolus
- Concurrent infections e.g., pnuemonia, viral illnesses
- Medication noncompliance
- Endocrine abnormalities - [[diabetes mellitus, thyroid disorders (hyperthyroidism, hypothyroidism)
Management
The algorithm below describes an approach to the management of patients with chronic heart failure.[12][13][14]
CHF | |||||||||||||||||||||||||||||||||
Control risk factors: ❑ | |||||||||||||||||||||||||||||||||
Fluid retention | No fluid retention | ||||||||||||||||||||||||||||||||
Diuretic therapy | ACE inhibitors AND Beta blockers | ||||||||||||||||||||||||||||||||
Intolerant to ACE-I | |||||||||||||||||||||||||||||||||
Cough | Renal insufficiency or angioedema | ||||||||||||||||||||||||||||||||
ARBs | Hydralazine/isosorbide dinitrate[15] | ||||||||||||||||||||||||||||||||
Persistent symptoms? | |||||||||||||||||||||||||||||||||
Yes | No | ||||||||||||||||||||||||||||||||
Add: ❑ Aldosterone or eplerenone
❑ Hydralazine/isosorbide dinitrate
| |||||||||||||||||||||||||||||||||
Persistent symptoms? | |||||||||||||||||||||||||||||||||
Add digoxin | |||||||||||||||||||||||||||||||||
Persistent symptoms? | |||||||||||||||||||||||||||||||||
Yes | No | ||||||||||||||||||||||||||||||||
LVEF ≤ 35%? | |||||||||||||||||||||||||||||||||
Yes | No | Yes | No | ||||||||||||||||||||||||||||||
Cardiac resynchronization therapy (CRT) ± Implantable cardioverter defibrillator (ICD) | Implantable cardioverter defibrillator | Continue GDMT | |||||||||||||||||||||||||||||||
Persistent symptoms | |||||||||||||||||||||||||||||||||
IV inotropes or vasodilators | |||||||||||||||||||||||||||||||||
Mechanical circulatory support[17]: ❑ LVAD - as bridge to recovery,[18] or as definitive therapy[19] | |||||||||||||||||||||||||||||||||
Cardiac transplantation | |||||||||||||||||||||||||||||||||
Commonly Prescribed Medications
Drug Class | Drug | Daily doses, maximum daily dose |
---|---|---|
Loop diuretics | Furosemide | 20 to 40 mg once or twice, 600 mg max daily dose In HF patients on loop diuretic, the initial IV dose should be greater or equal to their chronic oral daily dose.[20] |
Bumetanide | 0.5 to 1.0 mg once or twice, 10 mg | |
Torsemide | 10 to 20 mg once, 200 mg | |
Thiazide diuretics | Chlorothiazide | 250 to 500 mg once or twice, 1000 mg |
Hydrochlorothiazide | 25 mg once or twice, 200 mg | |
Metolazone | 2.5 mg once, 20 mg | |
K+- sparing diuretic | Amiloride | 5 mg once, 20 mg |
Spironolactone | 12.5 to 25.0 mg once, 50 mg | |
Triamterene | 50 to 75 mg twice, 200 mg | |
ACE inhibitors | Enalapril | 2.5 mg twice, 10 to 20 mg twice |
Lisinopril | 2.5 to 5 mg once, 20 to 40 mg once | |
Ramipril | 1.25 to 2.5 mg once, 10 mg once | |
ARBs | Candesartan | 4 to 8 mg once, 32 mg once |
Losartan | 25 to 50 mg once, 50 to 150 mg once | |
Valsartan | 20 to 40 mg twice, 160 mg twice | |
Beta blockers | Bisoprolol | 1.25 mg once, 10 mg once |
Carvedilol | 3.125 mg twice, 50 mg twice | |
Metoprolol succinate | 12.5 to 25.0 mg once, 200 mg once | |
Aldosterone antagonists | Spironolactone | 12.5 to 25.0 mg once, 25 mg once or twice |
Eplerenone | 25 mg once, 50 mg once | |
Inotropes | Dopamine | 5 to 10 mcg/kg/min |
Dobutamine | 2.5 to 5 mcg/kg/min | |
Milrinone | 0.125 to 0.75 mcg/kg/min | |
Vasodilators | Nitroglycerin | 5 to 10 mcg/min, increase dose by 5-10mcg/min every 3-5 mins as tolerated, max is 400mcg/min |
Nitroprusside | 5 to 10 mcg/min, increase dose by 5-10mcg/min every 5 mins as tolerated, max is 400mcg/min | |
Nesiritide | 2 mcg/kg bolus; then 0.01 mcg/kg/minute continuous infusion, maximum of 0.03 mcg/kg/minute | |
Hydralazine and isosorbide dinitrate | Fixed-dose combination | 37.5 mg hydralazine/20 mg isosorbide dinitrate 3 times daily, 75 mg hydralazine/40 mg isosorbide dinitrate 3 times daily |
Individual doses | Hydralazine: 25 to 50 mg 3 or 4 times daily, 300 mg daily in divided doses Isosorbide dinitrate: 20 to 30 mg 3 or 4 times daily, 120 mg daily in divided doses | |
Digoxin | 0.125 to 0.25 mg daily |
Diuretic Therapy
Evidence of volume overload | |||||||||||||||||||||
❑ Low sodium diet (<2 g daily)
Contraindications | |||||||||||||||||||||
Symptomatic improvement? | |||||||||||||||||||||
Yes | No | ||||||||||||||||||||
Maintain current IV diuretic dose | Double IV diuretic dose and titrate according to patient's response or when the maximum dose is reached | ||||||||||||||||||||
No symptomatic improvement | |||||||||||||||||||||
Add ❑ Another diuretic e.g., IV chlorothiazide or oral metolazone | Adjuvants to diuretics ❑ Low dose dopamine to preserve renal function and renal blood flow | ||||||||||||||||||||
No symptomatic improvement (refractory edema) | |||||||||||||||||||||
Ultrafiltration or dialysis | |||||||||||||||||||||
General measures ❑ Monitor BP, volume status, congestion ❑ Daily serum electrolytes, urea & creatinine ❑ DVT prophylaxis | |||||||||||||||||||||
Do's
- Order an echocardiogram as soon as possible if no recent one available or if the patient's clinical status is deteriorating.
- Digitalis decreases hospitalization but not mortality. It can be beneficial in symptomatic patients with low EF.[23][24][25][26][27][28][29]
- Make sure your patient is on DVT prophylaxis unless contraindicated.[30][31]
- Make use of aldosterone receptor antagonists (i.e. spironolactone or eplerenone) in patients with NYHA class II-IV and who have LVEF of 35% or less, unless contraindicated, to reduce morbidity and mortality. Patients with NYHA class II should have a history of prior cardiovascular hospitalization or elevated plasma natriuretic peptide levels to be considered for aldosterone receptor antagonists. Creatinine should be 2.5 mg/dL or less in men or 2.0 mg/dL or less in women (or estimated glomerular filtration rate >30 mL/min/1.73 m2), and potassium should be less than 5.0 mEq/L. Careful monitoring of potassium, renal function, and diuretic dosing should be performed at initiation and closely followed thereafter to minimize risk of hyperkalemia and renal insufficiency.[32][4][33]
- Start hydralazine and isosorbide dinitrate to reduce morbidity or mortality in patients with current or prior symptomatic HFrEF who cannot be given an ACE inhibitor or ARB because of drug intolerance, hypotension, or renal insufficiency, unless contraindicated. This combination has proven beneficial in African American population as well. [34][35][36][37][38]
- Consider adding another diuretic (e.g. metolazone or thiazides) for worsening congestion despite high doses of loop diuretics.[39][40]
- Daily serum electrolytes, urea nitrogen, and creatinine concentrations should be measured during the use of IV diuretics or active titration of heart failure medications.
- Use a combination of hydralazine and isosorbide dinitrate. They have been proven to reduce morbidity or mortality in patients with current or prior symptomatic HFrEF who cannot be given an ACE inhibitor or ARB because of drug intolerance, hypotension, or renal insufficiency, unless contraindicated.[41][42][43][44][45]
- Schedule an early follow-up visit (within 7 to 14 days) and early telephone follow-up (within 3 days) of hospital discharge .[46][47]
Don'ts
- If possible, don't order NSAIDs, sympathomimetics, tricyclic antidepressants, class I and III antiarrhythmics (except amiodarone), and nondihydropyridine calcium channel blockers (diltiazem, verapamil as they can cause harm in acute decompensated HF. [48][49][50][51][52][53][54]
- Don't Use parenteral inotropes in normotensive patients with acute decompensated HF without evidence of decreased organ perfusion. [55]
- Don't combine an ACEI, ARB, and aldosterone antagonist in patients with HFrEF unless otherwise indicated as this combination carries a risk of renal functions worsening and hyperkalemia.
- Don't use aldosterone receptor antagonists in patients with hyperkalemia or renal insufficiency when serum creatinine is more than 2.5 mg/dL in men or more than 2.0 mg/dL in women (or estimated glomerular filtration rate <30 mL/min/1.73 m2), and/or potassium more than 5.0 mEq/L.[56][57]
- Don't continue nutritional supplements with no proven benefit.
- Don't use statins routinely without other indications.[58][59]
References
- ↑ "Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). The CONSENSUS Trial Study Group". N Engl J Med. 316 (23): 1429–35. 1987. doi:10.1056/NEJM198706043162301. PMID 2883575.
- ↑ Garg R, Yusuf S (1995). "Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE Inhibitor Trials". JAMA. 273 (18): 1450–6. PMID 7654275.
- ↑ Foody JM, Farrell MH, Krumholz HM (2002). "beta-Blocker therapy in heart failure: scientific review". JAMA. 287 (7): 883–9. PMID 11851582.
- ↑ 4.0 4.1 Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H; et al. (2011). "Eplerenone in patients with systolic heart failure and mild symptoms". N Engl J Med. 364 (1): 11–21. doi:10.1056/NEJMoa1009492. PMID 21073363. Review in: J Fam Pract. 2011 Aug;60(8):482-4 Review in: Evid Based Med. 2011 Aug;16(4):121-2
- ↑ Cohn JN, Johnson G, Ziesche S, Cobb F, Francis G, Tristani F; et al. (1991). "A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure". N Engl J Med. 325 (5): 303–10. doi:10.1056/NEJM199108013250502. PMID 2057035.
- ↑ Gissi-HF Investigators. Tavazzi L, Maggioni AP, Marchioli R, Barlera S, Franzosi MG; et al. (2008). "Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial". Lancet. 372 (9645): 1223–30. doi:10.1016/S0140-6736(08)61239-8. PMID 18757090. Review in: Ann Intern Med. 2009 Jan 20;150(2):JC1-11
- ↑ Macchia A, Levantesi G, Franzosi MG, Geraci E, Maggioni AP, Marfisi R; et al. (2005). "Left ventricular systolic dysfunction, total mortality, and sudden death in patients with myocardial infarction treated with n-3 polyunsaturated fatty acids". Eur J Heart Fail. 7 (5): 904–9. doi:10.1016/j.ejheart.2005.04.008. PMID 16087142.
- ↑ Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L; et al. (2005). "The effect of cardiac resynchronization on morbidity and mortality in heart failure". N Engl J Med. 352 (15): 1539–49. doi:10.1056/NEJMoa050496. PMID 15753115. Review in: ACP J Club. 2005 Sep-Oct;143(2):29
- ↑ Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R; et al. (2005). "Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure". N Engl J Med. 352 (3): 225–37. doi:10.1056/NEJMoa043399. PMID 15659722. Review in: ACP J Club. 2005 Jul-Aug;143(1):6
- ↑ Digitalis Investigation Group (1997). "The effect of digoxin on mortality and morbidity in patients with heart failure". N Engl J Med. 336 (8): 525–33. doi:10.1056/NEJM199702203360801. PMID 9036306.
- ↑ Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ; et al. (2003). "Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial". Lancet. 362 (9386): 777–81. doi:10.1016/S0140-6736(03)14285-7. PMID 13678871. Review in: ACP J Club. 2004 Mar-Apr;140(2):32-3
- ↑ Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Drazner MH; et al. (2013). "2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines". Circulation. 128 (16): 1810–52. doi:10.1161/CIR.0b013e31829e8807. PMID 23741057.
- ↑ McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K; et al. (2012). "ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC". Eur Heart J. 33 (14): 1787–847. doi:10.1093/eurheartj/ehs104. PMID 22611136.
- ↑ Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG; et al. (2009). "2009 Focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation". J Am Coll Cardiol. 53 (15): e1–e90. doi:10.1016/j.jacc.2008.11.013. PMID 19358937.
- ↑ Cohn JN, Archibald DG, Ziesche S, Franciosa JA, Harston WE, Tristani FE; et al. (1986). "Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study". N Engl J Med. 314 (24): 1547–52. doi:10.1056/NEJM198606123142404. PMID 3520315.
- ↑ Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL; et al. (2003). "Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme". Lancet. 362 (9386): 759–66. PMID 13678868. Review in: ACP J Club. 2004 Mar-Apr;140(2):32-3
- ↑ Naidu SS (2011). "Novel percutaneous cardiac assist devices: the science of and indications for hemodynamic support". Circulation. 123 (5): 533–43. doi:10.1161/CIRCULATIONAHA.110.945055. PMID 21300961.
- ↑ Birks EJ, Tansley PD, Hardy J, George RS, Bowles CT, Burke M; et al. (2006). "Left ventricular assist device and drug therapy for the reversal of heart failure". N Engl J Med. 355 (18): 1873–84. doi:10.1056/NEJMoa053063. PMID 17079761.
- ↑ Slaughter MS, Rogers JG, Milano CA, Russell SD, Conte JV, Feldman D; et al. (2009). "Advanced heart failure treated with continuous-flow left ventricular assist device". N Engl J Med. 361 (23): 2241–51. doi:10.1056/NEJMoa0909938. PMID 19920051.
- ↑ Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, LeWinter MM, Deswal A, Rouleau JL, Ofili EO, Anstrom KJ, Hernandez AF, McNulty SE, Velazquez EJ, Kfoury AG, Chen HH, Givertz MM, Semigran MJ, Bart BA, Mascette AM, Braunwald E, O'Connor CM (2011). "Diuretic strategies in patients with acute decompensated heart failure". The New England Journal of Medicine. 364 (9): 797–805. doi:10.1056/NEJMoa1005419. PMC 3412356. PMID 21366472. Retrieved 2013-04-30. Unknown parameter
|month=
ignored (help) - ↑ Gheorghiade M, Gattis WA, O'Connor CM, Adams KF, Elkayam U, Barbagelata A; et al. (2004). "Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial". JAMA. 291 (16): 1963–71. doi:10.1001/jama.291.16.1963. PMID 15113814.
- ↑ Udelson JE, Smith WB, Hendrix GH, Painchaud CA, Ghazzi M, Thomas I; et al. (2001). "Acute hemodynamic effects of conivaptan, a dual V(1A) and V(2) vasopressin receptor antagonist, in patients with advanced heart failure". Circulation. 104 (20): 2417–23. PMID 11705818.
- ↑ The Captopril-Digoxin Multicenter Research Group. Comparative effects of therapy with captopril and digoxin in patients with mild to moderate heart failure. JAMA. 1988;259:539–44.
- ↑ Dobbs SM, Kenyon WI, Dobbs RJ. Maintenance digoxin after an episode of heart failure: placebo-controlled trial in outpatients. Br Med J. 1977;1:749–52
- ↑ Lee DC, Johnson RA, Bingham JB, et al. Heart failure in outpatients: a randomized trial of digoxin versus placebo. N Engl J Med. 1982;306: 699–705.
- ↑ Guyatt GH, Sullivan MJ, Fallen EL, et al. A controlled trial of digoxin in congestive heart failure. Am J Cardiol. 1988;61:371–5.
- ↑ . DiBianco R, Shabetai R, Kostuk W, et al. A comparison of oral milrinone, digoxin, and their combination in the treatment of patients with chronic heart failure. N Engl J Med. 1989;320:677–83.
- ↑ Uretsky BF, Young JB, Shahidi FE, et al., for the PROVED Investigative Group. Randomized study assessing the effect of digoxin withdrawal in patients with mild to moderate chronic congestive heart failure: results of the PROVED trial. J Am Coll Cardiol. 1993;22:955–62.
- ↑ Packer M, Gheorghiade M, Young JB, et al. Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-convertingenzyme inhibitors. RADIANCE Study. N Engl J Med. 1993;329:1–7.
- ↑ Alikhan R, Cohen AT, Combe S, Samama MM, Desjardins L, Eldor A; et al. (2003). "Prevention of venous thromboembolism in medical patients with enoxaparin: a subgroup analysis of the MEDENOX study". Blood Coagul Fibrinolysis. 14 (4): 341–6. PMID 12945875.
- ↑ Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ, American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis Panel (2012). "Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines". Chest. 141 (2 Suppl): 7S–47S. doi:10.1378/chest.1412S3. PMC 3278060. PMID 22315257.
- ↑ Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A; et al. (1999). "The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators". N Engl J Med. 341 (10): 709–17. doi:10.1056/NEJM199909023411001. PMID 10471456.
- ↑ Vizzardi E, D'Aloia A, Giubbini R, Bordonali T, Bugatti S, Pezzali N; et al. (2010). "Effect of spironolactone on left ventricular ejection fraction and volumes in patients with class I or II heart failure". Am J Cardiol. 106 (9): 1292–6. doi:10.1016/j.amjcard.2010.06.052. PMID 21029826.
- ↑ Carson P, Ziesche S, Johnson G, et al., for the 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;5:178–87.
- ↑ Cohn JN. The Vasodilator-Heart Failure Trials (V-HeFT). Mechanistic data from the VA Cooperative Studies. Introduction. Circulation. 1993; 87:VI1–4.
- ↑ Carson P, Ziesche S, Johnson G, et al., for the 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;5:178–87.
- ↑ Cohn JN, Archibald DG, Ziesche S, et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study. N Engl J Med. 1986;314:1547–52.
- ↑ Loeb HS, Johnson G, Henrick A, et al., for the V-HeFT VA Cooperative Studies Group. Effect of enalapril, hydralazine plus isosorbide dinitrate, and prazosin on hospitalization in patients with chronic congestive heart failure. Circulation. 1993;87:VI78–87.
- ↑ Grosskopf I, Rabinovitz M, Rosenfeld JB (1986). "Combination of furosemide and metolazone in the treatment of severe congestive heart failure". Isr J Med Sci. 22 (11): 787–90. PMID 3793436.
- ↑ Rosenberg J, Gustafsson F, Galatius S, Hildebrandt PR (2005). "Combination therapy with metolazone and loop diuretics in outpatients with refractory heart failure: an observational study and review of the literature". Cardiovasc Drugs Ther. 19 (4): 301–6. doi:10.1007/s10557-005-3350-2. PMID 16189620.
- ↑ Carson P, Ziesche S, Johnson G, et al., for the 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;5:178–87.
- ↑ Cohn JN. The Vasodilator-Heart Failure Trials (V-HeFT). Mechanistic data from the VA Cooperative Studies. Introduction. Circulation. 1993; 87:VI1–4.
- ↑ Carson P, Ziesche S, Johnson G, et al., for the 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;5:178–87.
- ↑ Cohn JN, Archibald DG, Ziesche S, et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study. N Engl J Med. 1986;314:1547–52.
- ↑ Loeb HS, Johnson G, Henrick A, et al., for the V-HeFT VA Cooperative Studies Group. Effect of enalapril, hydralazine plus isosorbide dinitrate, and prazosin on hospitalization in patients with chronic congestive heart failure. Circulation. 1993;87:VI78–87.
- ↑ Krumholz HM, Chen YT, Wang Y, Vaccarino V, Radford MJ, Horwitz RI (2000). "Predictors of readmission among elderly survivors of admission with heart failure". Am Heart J. 139 (1 Pt 1): 72–7. PMID 10618565.
- ↑ Hernandez AF, Greiner MA, Fonarow GC, Hammill BG, Heidenreich PA, Yancy CW; et al. (2010). "Relationship between early physician follow-up and 30-day readmission among Medicare beneficiaries hospitalized for heart failure". JAMA. 303 (17): 1716–22. doi:10.1001/jama.2010.533. PMID 20442387.
- ↑ Heerdink ER, Leufkens HG, Herings RM, et al. NSAIDs associated with increased risk of congestive heart failure in elderly patients taking diuretics. Arch Intern Med. 1998;158:1108–12.
- ↑ . Herchuelz A, Derenne F, Deger F, et al. Interaction between nonsteroidal anti-inflammatory drugs and loop diuretics: modulation by sodiumbalance. J Pharmacol Exp Ther. 1989;248:1175–81.
- ↑ Gottlieb SS, Robinson S, Krichten CM, et al. Renal response to indomethacin in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 1992;70:890–3
- ↑ Bank AJ, Kubo SH, Rector TS, et al. Local forearm vasodilation with intra-arterial administration of enalaprilat in humans. Clin Pharmacol Ther. 1991;50:314–21.
- ↑ The Cardiac Arrhythmia Suppression Trial (CAST) Investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med. 1989;321:406–12.
- ↑ The Cardiac Arrhythmia Suppression Trial II Investigators. Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. N Engl J Med. 1992;327:227–33.
- ↑ Pratt CM, Eaton T, Francis M, et al. The inverse relationship between baseline left ventricular ejection fraction and outcome of antiarrhythmic therapy: a dangerous imbalance in the risk-benefit ratio. Am Heart J. 1989;118:433–40.
- ↑ Cuffe MS, Califf RM, Adams KF, Benza R, Bourge R, Colucci WS, Massie BM, O'Connor CM, Pina I, Quigg R, Silver MA, Gheorghiade M (2002). "Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a randomized controlled trial". JAMA : the Journal of the American Medical Association. 287 (12): 1541–7. PMID 11911756. Retrieved 2012-04-06. Unknown parameter
|month=
ignored (help) - ↑ Juurlink DN, Mamdani MM, Lee DS, Kopp A, Austin PC, Laupacis A; et al. (2004). "Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study". N Engl J Med. 351 (6): 543–51. doi:10.1056/NEJMoa040135. PMID 15295047.
- ↑ Bozkurt B, Agoston I, Knowlton AA (2003). "Complications of inappropriate use of spironolactone in heart failure: when an old medicine spirals out of new guidelines". J Am Coll Cardiol. 41 (2): 211–4. PMID 12535810.
- ↑ Horwich TB, MacLellan WR, Fonarow GC (2004). "Statin therapy is associated with improved survival in ischemic and non-ischemic heart failure". J Am Coll Cardiol. 43 (4): 642–8. doi:10.1016/j.jacc.2003.07.049. PMID 14975476.
- ↑ Gissi-HF Investigators. Tavazzi L, Maggioni AP, Marchioli R, Barlera S, Franzosi MG; et al. (2008). "Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial". Lancet. 372 (9645): 1231–9. doi:10.1016/S0140-6736(08)61240-4. PMID 18757089.
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