Clinical event adjudication: Heart failure requiring hospitalization

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Editors-in-Chief: C. Michael Gibson, M.S., M.D. [1]

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This chapter presents heart failure requiring hospitalization definitions used in the Clinical Event Committee adjudication processes. These definitions are current as of 3/26/10.

Heart failure requiring hospitalization

Heart failure (HF) requiring hospitalization is defined as an event that meets the following criteria:

  1. Requires hospitalization defined as an admission to an inpatient unit or a visit to an emergency department that results in at least a 24* hour stay (or a date change if the time of
    admission/discharge is not available).
    *For this endpoint in any given clinical trial, there should be some flexibility in the required duration of stay, depending on the population and the adverse event profile of the drug to be studied. For example, a clinical trial studying patients with NYHA Class III/IV heart failure may not wish to capture hospitalizations less than 24 hours in duration, because this population may have frequent hospital visits requiring short-term therapy. On the contrary, clinical trials in patients with NYHA Class I/II heart failure may wish to capture shorter hospitalizations that may be predictive of subsequent decompensation.
    AND
  2. Clinical symptoms of heart failure, including at least one of the following:
    New or worsening
    • dyspnea
    • orthopnea
    • paroxysmal nocturnal dyspnea
    • increasing fatigue/worsening exercise tolerance
      AND
  3. Physical signs of heart failure, including at least two of the following:
    • edema (greater than 2+ lower extremity)
    • pulmonary crackles greater than basilar (pulmonary edema must be sufficient to cause tachypnea and distress not occurring in the context of an acute myocardial infarction or as the consequence of an arrhythmia occurring in the absence of worsening heart failure)
    • jugular venous distension
    • tachypnea (respiratory rate > 20 breaths/minute)
    • rapid weight gain
    • S3 gallop
    • increasing abdominal distension or ascites
    • hepatojugular reflux
    • radiological evidence of worsening heart failure
    • A right heart catheterization within 24 hours of admission showing a pulmonary capillary wedge pressure (pulmonary artery occlusion pressure) ≥ 18 mm Hg or a cardiac output < 2.2 L/min/m2

      NOTE: Biomarker results (e.g., brain natriuretic peptide (BNP)) consistent with congestive heart failure will be supportive of this diagnosis, but the elevation in BNP cannot be due to other conditions such as cor pulmonale, pulmonary embolus, primary pulmonary hypertension, or congenital heart disease. Increasing levels of BNP, although not exceeding the ULN, may also be supportive of the diagnosis of congestive heart failure in selected cases (e.g. morbid obesity).

      AND

  4. Need for additional/increased therapy
    • Initiation of, or an increase in, treatment directed at heart failure or occurring in a patient already receiving maximal therapy for heart failure and including at least one of the following:
      • Initiation of or a significant augmentation in oral therapy for the treatment of congestive heart failure
      • Initiation of intravenous diuretic, inotrope, or vasodilator therapy
      • Uptitration of intravenous therapy, if already on therapy
      • Initiation of mechanical or surgical intervention (mechanical circulatory support, heart transplantation or ventricular pacing to improve cardiac function), or the use of ultrafiltration, hemofiltration, or dialysis that is specifically directed at treatment of heart failure.
        AND
5. No other non-cardiac etiology (such as chronic obstructive pulmonary disease, hepatic cirrhosis, acute renal failure, or venous insufficiency) and no other cardiac etiology (such as pulmonary embolus, cor pulmonale, primary pulmonary hypertension, or congenital heart disease) for signs or symptoms is identified.

NOTE: It is recognized that some patients may have multiple simultaneous disease processes. Nevertheless, for the endpoint event of heart failure requiring hospitalization, the diagnosis of congestive heart failure would need to be the primary disease process accounting for the above signs and symptoms.

References

  1. ACC/AHA 2007 Guidelines for the Management of Patients with Unstable Angina/Non ST-Elevation Myocardial Infarction: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction): Developed in Collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons: Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine, Circulation, 2007, 116:803-877.
  2. Campeau L, Grading of angina pectoris (letter), Circulation, 1976, 54:522-23.
  3. Cutlip DE, S Windecker, R Mehran, A Boam, DJ Cohen, G-A van Es, PG Steg, M-A Morel, L Mauri, P Vranckx, E McFadden, A Lansky, M Hamon, MW Krucoff, PW Serruys and on behalf of the Academic Research Consortium, Clinical End Points in Coronary Stent Trials: A Case for Standardized Definitions, Circulation, 2007, 115:2344-2351.
  4. Easton JD, Saver JL, Albers GW, Alberts MJ, Chaturvedi S, Feldmann E, Hatsukami TS, Higashida RT, Johnston SC, Kidwell CS, Lutsep HL, Miller E, Sacco RL; Definition and Evaluation of Transient Ischemic Attack, A Scientific Statement for Healthcare Professionals from the American Heart Association; American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease, Stroke, 2009 Jun; 40(6):2276-93. Epub 2009 May 7. Review.
  5. Thygesen, Kristian, Alpert JS, White HD on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. Universal Definition of Myocardial Infarction, Circulation, 2007, 116:1-20.