Author + information
- Anuradha Lala, MD and
- Judith S. Hochman, MD∗ ()
- ↵∗Reprint requests and correspondence:
Dr. Judith S. Hochman, New York University School of Medicine, Department of Medicine, 530 First Avenue, Skirball 9R, New York, New York 10016.
- acute myocardial infarction (MI)
- cardiogenic shock
- coronary care unit (CCU)
- heart failure
- Killip classification
In 1967, Dr. Thomas Killip and Dr. John Kimball (1) reported their experience with a novel construct called the coronary care unit to cluster and care for patients with suspected acute myocardial infarction (MI). “To provide a clinical estimate of the severity of myocardial derangement,” they classified patients into one of four categories: 1) no heart failure (HF); 2) HF as demonstrated by the presence of rales, an S3 gallop, and/or venous hypertension; 3) severe HF or frank pulmonary edema; and 4) cardiogenic shock.
In their study of 250 patients, one-third were free from HF symptoms, another third had evidence of HF, and one-third had frank pulmonary edema or cardiogenic shock. This system later became known as the Killip classification, which we still use today. Its implementation in practice has since evolved to guide management and prognosticate while serving as an important tool for tracking outcomes in clinical research. Simply put, we learned that if and when HF complicates acute MI, even if manifested only by basilar rales, prognosis markedly worsens.
A number of advances in cardiovascular medicine have conferred reduced mortality for patients with acute MIs over the past 50 years. The advent of the coronary care unit has afforded specialized care and appropriate monitoring. Reperfusion therapy has led to reductions in infarct size and mortality, and several medications have been shown to be lifesaving. How we diagnose acute MI has also changed, with increasingly sensitive biomarkers being used. What was previously diagnosed as unstable angina is now often diagnosed as MI. As such, patients with MIs today are of a different phenotype than they once were. They are older, they are more obese, with an increasing proportion of women, and they have a greater number of comorbid conditions (2,3).
Coronary artery disease is the most important risk factor for the development of HF, seen most dramatically via acute MI presentation and captured in the Killip classification (4). HF may result from a reduction in contractility as a result of infarcted, stunned, or ischemic myocardium, ischemia-induced or pre-existing other causes of diastolic dysfunction, or the development of mitral regurgitation (5). Epidemiologic studies do not make a distinction between HF with reduced ejection fraction and HF with preserved ejection fraction, however. With improved MI management and medical therapy to combat neurohormonal activation, HF now spans a wide spectrum of disease, ranging from acute decompensation to a chronic asymptomatic state. Its increased prevalence serves as a staggering economic and public health burden worldwide (6).
So how do these 2 disease states that are so closely related but also independent of each other interplay in the modern era of coronary care unit care, percutaneous coronary intervention technology, and effective medical therapy?
In this issue of JACC: Heart Failure, Desta et al. (7) report an examination of this relationship using the SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies)/RIKS-HIA (Register of Information and Knowledge About Swedish Heart Intensive Care Admissions) registry, which includes 72 hospitals and collects a wide array of patient information prospectively. The merging of coexisting databases of the RIKS-HIA and National Patient Register enabled diagnosis and follow-up outcomes for a large number of patients over a 13-year time period. HF was defined by the presence of rales, need for intravenous diuretic agents, continuous positive airway pressure, and/or inotropes, and Killip class–determined severity. From 1997 to 2008, the average age, proportion of women, prevalence of diabetes, and proportion of smokers increased marginally, while the diagnosis of hypertension increased and history of MI or HF decreased substantially.
The incidence of HF during an index hospitalization for MI decreased by 39% (an absolute reduction of 18%) over the study period. In these patients, an increasing proportion was diagnosed with HF with preserved ejection fraction, whereas the frequency of HF with reduced ejection fraction decreased slightly. As one would expect, the implementation of medical therapy, particularly of thienopyridines (clopidogrel) and statins, as well as percutaneous coronary intervention therapy increased over time. Despite declines in the incidence of HF complicating acute MI as well as in-hospital, 30-day, and 1-year mortality for these patients, a 2-fold greater risk for death was observed in long-term survival analysis compared with patients with MIs without HF (hazard ratio: 2.09; 95% confidence interval: 2.06 to 2.13).
The investigators are to be commended for conducting a large-scale study, through the use of a nationwide registry that collects detailed information prospectively coupled with robust follow-up and outcome data. Inherent limitations are present in any observational study, however. The definition of HF can be complicated, and cases may have been missed by not assessing other commonly used signs reflecting congestion, such as elevated jugular venous pressure, orthopnea, and natriuretic peptide levels. As the investigators mention, because of a change in the definition of MI between 2001 and 2002, an increased number of MIs may have been detected in the latter part of the study, affecting results. This dataset also did not capture aldosterone antagonist use, which is likely particularly relevant given the all-cause mortality reduction seen for MI with signs of HF or diabetes mellitus in EPHESUS (Epleronone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study) (8).
Interestingly, the survival advantage from 1996 to 2008 demonstrated for patients with HF during hospitalization for acute MI is appreciated early on, without apparent increasing benefit seen over time. If guideline-indicated medical and device therapies were broadly used, one would expect Kaplan-Meier survival curves that continue to diverge. Information on discharge medications, outpatient adherence, and device therapy for patients with HF is not provided. Nonetheless, though not all trends may be generalizable given the largely homogeneous population in which the study was conducted, it appears what was observed nearly 50 years ago still holds true today: patients with acute MIs with HF have markedly worse outcomes compared with those without HF.
What is the significance of these findings? The continued use of the Killip classification helps identify a high-risk group for whom specific therapies need to be targeted. Patients with HF symptoms after MI (i.e., Killip class II or greater) likely require triage to a higher level of care while in the hospital, meticulous attention to guideline-directed medical therapy, and closer post-discharge follow-up to prevent adverse outcomes. Despite significant changes in the epidemiology, presentation, and improved outcomes in acute MI and HF, the Killip classification has maintained its prognostic utility for half a century after its inception. Sometimes, the more things change, the more they stay the same.
↵∗ Editorials published in JACC: Heart Failure reflect the views of the authors and do not necessarily represent the views of JACC: Heart Failure or the American College of Cardiology.
Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
- Go A.S.,
- Mozaffarian D.,
- Roger V.L.,
- et al.
- Lloyd-Jones D.M.,
- Larson M.G.,
- Leip E.P.,
- et al.
- Gheorghiade M.,
- Sopko G.,
- De Luca L.,
- et al.
- Braunwald E.
- Desta L.,
- Jernberg T.,
- Löfman I.,
- et al.