Congestive heart failure positive inotropics
Congestive heart failure Microchapters
ACC/AHA Guideline Recommendations:
Congestive heart failure positive inotropics On the Web
Positive inotropes are agents that increase myocardial contractility, and are used to support cardiac function in conditions such as decompensated congestive heart failure, cardiogenic shock, septic shock, myocardial infarction, cardiomyopathy, etc. Examples of positive inotropes include digoxin, dobutamine, dopamine and phosphodiesterase-III inhibitors like amrinone and milrinone.
- Agents that increase intracellular cAMP
- Alpha-adrenergic agonists
- Phosphodiesterase inhibitors
- Agents that affect sarcolemmal ion pumps/channels
- Agents that modulate intracellular calcium mechanisms by either:
- Drugs having multiple mechanisms of action
- Inhibits Na,K+-ATPase resulting in an increase in intracellular Na+, extracellular Ca2+ exchange increasing the velocity and extent of sarcomere shortening.
- ACC/AHA recommend digoxin for symptomatic patients with left ventricular systolic dysfunction.
- Commonly used in patients with heart failure and atrial fibrillation to reduce the ventricular response rate.
- Mortality has not been shown to be improved with use of digoxin, but the use of digoxin has been associated with a reduction in hospitalization in the RALES study.
- There is no need to load a CHF patient with digoxin. For the majority of patients with normal renal function, a daily dose of 0.25 mg of digoxin is usually adequate. In the older patient or in those patients with renal impairment, a dose of 0.125 mg per day may be adequate.
- Drugs that increase the concentration of digoxin include antibiotics and anticholinergic agents as well as amiodarone, quinidine and verapamil.
- In the RALES study, a level of < 1 ng/ml was associated with efficacy. Levels above 1 ng/ml were not associated with greater efficacy and were associated with higher mortality.
- Activates beta-1 receptors resulting in enhanced cardiac contractility.
- Long-term dobutamine infusions are arrhythmogenic and increase mortality.
- Dobutamine also slightly reduces afterload
Dopamine is associated with a dose dependent mechanism of action:
- At low doses: (≤2 µg/kg/min), selectively dilate splanchnic and renal arterial beds and increase renal perfusion.
- At intermediate doses: (2 to 10 µg/kg/min), increase norepinephrine secretion and result in increased cardiac contractility, heart rate and systemic vascular resistance.
- At higher doses: (5 to 20 µg/kg/min), result in direct alpha-adrenergic receptor stimulation and increases systemic vascular resistance.
- Phosphodiesterase-III inhibitor that enhances cardiac contractility by increasing intracellular cyclic adenosine monophosphate (cAMP).
- Potent pulmonary vasodilator that may benefit some patients with pulmonary hypertension.
- Unlike dobutamine, milrinone is beneficial in decompensated heart failure patients who are on beta-blocker therapy.
- Long term milrinone infusions are arrhythmogenic, and increase mortality.
2009 ACC/AHA Focused Update and 2005 Guidelines for the Diagnosis and Management of Chronic Heart Failure in the Adult (DO NOT EDIT) 
|Class III (No Benefit)|
|"'1. Long-term use of an infusion of a positive inotropic drug may be harmful and is not recommended for patients with current or prior symptoms of heart failure and reduced left ventricular ejection fraction (LVEF), except as palliation for patients with end-stage disease who cannot be stabilized with standard medical treatment. (Level of Evidence: C) "|
|"1. Digitalis can be beneﬁcial in patients with current or prior symptoms of heart failure and reduced left ventricular ejection fraction (LVEF) to decrease hospitalizations for heart failure.  (Level of Evidence: B) "|
- ↑ 1.0 1.1 (February 1997) "The effect of digoxin on mortality and morbidity in patients with heart failure. The Digitalis Investigation Group". The New England Journal of Medicine 336 (8): 525–33. doi:10.1056/NEJM199702203360801. PMID 9036306. Retrieved on 2012-04-05.
- ↑ 2.0 2.1 2.2 Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, Oates JA, Rahko PS, Silver MA, Stevenson LW, Yancy CW, Antman EM, Smith SC Jr, Adams CD, Anderson JL, Faxon DP, Fuster V, Halperin JL, Hiratzka LF, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; American College of Chest Physicians; International Society for Heart and Lung Transplantation; Heart Rhythm Society. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Circulation. 2005 Sep 20; 112(12): e154-235. Epub 2005 Sep 13. PMID 16160202
- ↑ 3.0 3.1 3.2 Jessup M, Abraham WT, Casey DE, Feldman AM, Francis GS, Ganiats TG et al. (2009) 2009 focused update: ACCF/AHA 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. Circulation 119 (14):1977-2016. DOI:10.1161/CIRCULATIONAHA.109.192064 PMID: 19324967
- ↑ (1988) "Comparative effects of therapy with captopril and digoxin in patients with mild to moderate heart failure. The Captopril-Digoxin Multicenter Research Group". JAMA : the Journal of the American Medical Association 259 (4): 539–44. PMID 2447297. Retrieved on 2012-04-05.
- ↑ Dobbs SM, Kenyon WI, Dobbs RJ (March 1977). "Maintenance digoxin after an episode of heart failure: placebo-controlled trial in outpatients". British Medical Journal 1 (6063): 749–52. PMID 322793. Retrieved on 2012-04-05.
- ↑ Lee DC, Johnson RA, Bingham JB, Leahy M, Dinsmore RE, Goroll AH, Newell JB, Strauss HW, Haber E (March 1982). "Heart failure in outpatients: a randomized trial of digoxin versus placebo". The New England Journal of Medicine 306 (12): 699–705. doi:10.1056/NEJM198203253061202. PMID 7038483. Retrieved on 2012-04-05.
- ↑ Guyatt GH, Sullivan MJ, Fallen EL, Tihal H, Rideout E, Halcrow S, Nogradi S, Townsend M, Taylor DW (February 1988). "A controlled trial of digoxin in congestive heart failure". The American Journal of Cardiology 61 (4): 371–5. PMID 3277366. Retrieved on 2012-04-05.
- ↑ DiBianco R, Shabetai R, Kostuk W, Moran J, Schlant RC, Wright R (March 1989). "A comparison of oral milrinone, digoxin, and their combination in the treatment of patients with chronic heart failure". The New England Journal of Medicine 320 (11): 677–83. doi:10.1056/NEJM198903163201101. PMID 2646536. Retrieved on 2012-04-05.
- ↑ Uretsky BF, Young JB, Shahidi FE, Yellen LG, Harrison MC, Jolly MK (October 1993). "Randomized study assessing the effect of digoxin withdrawal in patients with mild to moderate chronic congestive heart failure: results of the PROVED trial. PROVED Investigative Group". Journal of the American College of Cardiology 22 (4): 955–62. PMID 8409069. Retrieved on 2012-04-05.
- ↑ Packer M, Gheorghiade M, Young JB, Costantini PJ, Adams KF, Cody RJ, Smith LK, Van Voorhees L, Gourley LA, Jolly MK (July 1993). "Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-converting-enzyme inhibitors. RADIANCE Study". The New England Journal of Medicine 329 (1): 1–7. doi:10.1056/NEJM199307013290101. PMID 8505940. Retrieved on 2012-04-05.
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