Canadian Journal of Cardiology

Arrhythmic events and mortality in patients with cardiogenic shock on inotropic support: results of the DOREMI randomized trial

Published:September 20, 2022DOI:



      Inotropic support is widely used in the management of cardiogenic shock (CS). Existing data on the incidence and significance of arrhythmic events in patients with CS on inotropic support is at high risk of bias.


      The DObutamine compaREd to MIlrinone (DOREMI) trial randomized patients to receive dobutamine or milrinone in a double-blind fashion. Patients with and without arrhythmic events (defined as arrhythmias requiring intervention or sustained ventricular arrhythmias) were compared to (1) identify factors associated with their occurrence and (2) examine their association with in-hospital mortality and secondary outcomes.


      Ninety-two patients (47.9%) had arrhythmic events, occurring equally with dobutamine and milrinone (P=0.563). The need for vasopressor support at inotrope initiation and a history of atrial fibrillation were positively associated with arrhythmic events whereas predominant right ventricular dysfunction, previous myocardial infarction, and increasing left ventricular ejection fraction were negatively associated with them. Supraventricular arrhythmic events were not associated with mortality (RR 0.97, 95% CI 0.68-1.40, P=0.879) but were positively associated with resuscitated cardiac arrests and hospital length of stay. Ventricular arrhythmic events were positively associated with mortality (RR 1.66, 95% CI 1.13-2.43; P=0.026) and resuscitated cardiac arrests. Arrhythmic events were most often treated with amiodarone (97%) and electrical cardioversion (27%), which were not associated with mortality.


      Clinically relevant arrhythmic events occur in approximately half of patients with CS treated with dobutamine or milrinone and are associated with adverse clinical outcomes. Five factors may help identify patients most at risk of arrhythmic events.

      Graphical abstract

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Canadian Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Mathew R.
        • Visintini S.M.
        • Ramirez F.D.
        • et al.
        Efficacy of milrinone and dobutamine in low cardiac output states: Systematic review and meta-analysis.
        Clin Invest Med. 2019; 42: E26-32
        • Aranda Jr., J.M.
        • Schofield R.S.
        • Pauly D.F.
        • et al.
        Comparison of dobutamine versus milrinone therapy in hospitalized patients awaiting cardiac transplantation: a prospective, randomized trial.
        Am Heart J. 2003; 145: 324-329
        • Yamani M.H.
        • Haji S.A.
        • Starling R.C.
        • et al.
        Comparison of dobutamine-based and milrinone-based therapy for advanced decompensated congestive heart failure: Hemodynamic efficacy, clinical outcome, and economic impact.
        Am Heart J. 2001; 142: 998-1002
        • Lewis T.C.
        • Aberle C.
        • Altshuler D.
        • Piper G.L.
        • Papadopoulos J.
        Comparative Effectiveness and Safety Between Milrinone or Dobutamine as Initial Inotrope Therapy in Cardiogenic Shock.
        J Cardiovasc Pharmacol Ther. 2019; 24: 130-138
        • Harhash A.A.
        • Cassuto J.
        • Hussein A.
        • et al.
        Safety of Outpatient Milrinone Infusion in End-Stage Heart Failure: ICD-Level Data on Atrial Fibrillation and Ventricular Tachyarrhythmias.
        Am J Med. 2020; 133: 857-864
        • Mathew R.
        • Di Santo P.
        • Jung R.G.
        • et al.
        Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock.
        N Engl J Med. 2021; 385: 516-525
        • Thiele H.
        • Zeymer U.
        • Neumann F.J.
        • et al.
        Intraaortic balloon support for myocardial infarction with cardiogenic shock.
        N Engl J Med. 2012; 367: 1287-1296
        • Tehrani B.N.
        • Drakos S.G.
        • Billia F.
        • et al.
        The Multicenter Collaborative to Enhance Biologic Understanding, Quality, and Outcomes in Cardiogenic Shock (VANQUISH Shock): Rationale and Design.
        Can J Cardiol. 2022; 38: 1286-1295
        • Francis G.S.
        • Bartos J.A.
        • Adatya S.
        Inotropes. J Am Coll Cardiol. 2014; 63: 2069-2078
        • Colucci W.S.
        • Wright R.F.
        • Jaski B.E.
        • Fifer M.A.
        • Braunwald E.
        Milrinone and dobutamine in severe heart failure: differing hemodynamic effects and individual patient responsiveness.
        Circulation. 1986; 73: III175-183
        • Vallabhajosyula S.
        • Patlolla S.H.
        • Verghese D.
        • et al.
        Burden of Arrhythmias in Acute Myocardial Infarction Complicated by Cardiogenic Shock.
        Am J Cardiol. 2020; 125: 1774-1781
        • Levy B.
        • Clere-Jehl R.
        • Legras A.
        • et al.
        Epinephrine Versus Norepinephrine for Cardiogenic Shock After Acute Myocardial Infarction.
        J Am Coll Cardiol. 2018; 72: 173-182
        • Jeger R.V.
        • Assmann S.F.
        • Yehudai L.
        • Ramanathan K.
        • Farkouh M.E.
        • Hochman J.S.
        Causes of death and re-hospitalization in cardiogenic shock.
        Acute Card Care. 2007; 9: 25-33
        • de Waha S.
        • Schoene K.
        • Fuernau G.
        • et al.
        Prognostic impact of atrial fibrillation in cardiogenic shock complicating acute myocardial infarction: a substudy of the IABP-SHOCK II trial.
        Clin Res Cardiol. 2018; 107: 233-240
        • Cuffe M.S.
        • Califf R.M.
        • Adams Jr., K.F.
        • et al.
        Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a randomized controlled trial.
        JAMA. 2002; 287: 1541-1547
        • Di Santo P.
        • Mathew R.
        • Jung R.G.
        • et al.
        Impact of baseline beta-blocker use on inotrope response and clinical outcomes in cardiogenic shock: a subgroup analysis of the DOREMI trial.
        Crit Care. 2021; 25: 289
        • Bennett M.
        • Parkash R.
        • Nery P.
        • et al.
        Canadian Cardiovascular Society/Canadian Heart Rhythm Society 2016 Implantable Cardioverter-Defibrillator Guidelines.
        Can J Cardiol. 2017; 33: 174-188
        • Parlow S.
        • Di Santo P.
        • Mathew R.
        • et al.
        The association between mean arterial pressure and outcomes in patients with cardiogenic shock: insights from the DOREMI trial.
        Eur Heart J Acute Cardiovasc Care. 2021;
        • Malasana G.
        • Daccarett M.
        • Kuppahally S.
        • Wasmund S.L.
        • Litwin S.E.
        • Hamdan M.H.
        High prevalence of right ventricular dysfunction in ICD patients with shocks: a potential new predictor in risk stratification.
        J Interv Card Electrophysiol. 2011; 31: 165-169
        • Aktas M.K.
        • Kim D.D.
        • McNitt S.
        • et al.
        Right ventricular dysfunction and the incidence of implantable cardioverter-defibrillator therapies.
        Pacing Clin Electrophysiol. 2009; 32: 1501-1508
        • Naksuk N.
        • Tan N.
        • Padmanabhan D.
        • et al.
        Right Ventricular Dysfunction and Long-Term Risk of Sudden Cardiac Death in Patients With and Without Severe Left Ventricular Dysfunction.
        Circulation. Arrhythmia and electrophysiology. 2018; 11e006091
        • Mikami Y.
        • Jolly U.
        • Heydari B.
        • et al.
        Right Ventricular Ejection Fraction Is Incremental to Left Ventricular Ejection Fraction for the Prediction of Future Arrhythmic Events in Patients With Systolic Dysfunction.
        Circulation. Arrhythmia and electrophysiology. 2017; 10
        • Elming M.B.
        • Hammer-Hansen S.
        • Voges I.
        • et al.
        Right Ventricular Dysfunction and the Effect of Defibrillator Implantation in Patients With Nonischemic Systolic Heart Failure.
        Circulation. Arrhythmia and electrophysiology. 2019; 12e007022
        • Purmah Y.
        • Lei L.Y.
        • Dykstra S.
        • et al.
        Right Ventricular Ejection Fraction for the Prediction of Major Adverse Cardiovascular and Heart Failure-Related Events: A Cardiac MRI Based Study of 7131 Patients With Known or Suspected Cardiovascular Disease.
        Circ Cardiovasc Imaging. 2021; 14e011337
        • Chatterjee N.A.
        • Shah R.V.
        • Murthy V.L.
        • et al.
        Right Ventricular Structure and Function Are Associated With Incident Atrial Fibrillation: MESA-RV Study (Multi-Ethnic Study of Atherosclerosis-Right Ventricle).
        Circulation. Arrhythmia and electrophysiology. 2017; 10
        • Konstam M.A.
        • Kiernan M.S.
        • Bernstein D.
        • et al.
        Evaluation and Management of Right-Sided Heart Failure: A Scientific Statement From the American Heart Association.
        Circulation. 2018; 137: e578-e622
        • Felker G.M.
        • Benza R.L.
        • Chandler A.B.
        • et al.
        Heart failure etiology and response to milrinone in decompensated heart failure: results from the OPTIME-CHF study.
        J Am Coll Cardiol. 2003; 41: 997-1003
        • Parlow S.
        • Weng W.
        • Di Santo P.
        • et al.
        Significant Valvular Dysfunction and Outcomes in Cardiogenic Shock: Insights From the Randomized DOREMI Trial.
        Can J Cardiol. 2022; 38: 1211-1219
        • Echt D.S.
        • Liebson P.R.
        • Mitchell L.B.
        • et al.
        Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial.
        N Engl J Med. 1991; 324: 781-788
        • Peduzzi P.
        • Concato J.
        • Kemper E.
        • Holford T.R.
        • Feinstein A.R.
        A simulation study of the number of events per variable in logistic regression analysis.
        J Clin Epidemiol. 1996; 49: 1373-1379
        • Althouse A.D.
        • Below J.E.
        • Claggett B.L.
        • et al.
        Recommendations for Statistical Reporting in Cardiovascular Medicine: A Special Report From the American Heart Association.
        Circulation. 2021; 144: e70-e91
        • Gaies M.G.
        • Gurney J.G.
        • Yen A.H.
        • et al.
        Vasoactive-inotropic score as a predictor of morbidity and mortality in infants after cardiopulmonary bypass.
        Pediatr Crit Care Med. 2010; 11: 234-238