Author + information
- Carolyn S.P. Lam, MBBS∗ ()
- ↵∗National University Health System, Tower Block Level 9, 1E Kent Ridge Road, Singapore 119228
We have come a long way in the diastolic heart failure (HF)—HF with normal systolic function—HF with normal ejection fraction (EF)—HF with preserved EF world (1). Just 2 decades ago, we couldn’t agree whether this syndrome existed. This skepticism has been replaced by general recognition that it not only exists, but that it constitutes a sizeable proportion of the HF population and is a deadly disease. However, this is where the consensus seems to end—we can’t agree on what to call it, nor if it is a distinct syndrome or part of the same continuous spectrum as HF with reduced EF (HFrEF).
Perhaps the purest description of this syndrome was the first by Topol et al. (2) in 1985, where the term hypertensive hypertrophic cardiomyopathy of the elderly was used to describe 21 elderly, predominantly female hypertensive patients with HF symptoms, left ventricular (LV) hypertrophy, high EF, and diastolic dysfunction. Robust epidemiological evidence has confirmed that this is a condition predominantly affecting elderly hypertensive women.
The term diastolic HF was coined to underscore the hallmark of LV diastolic dysfunction seen in most, if not all, patients. The diastolic/systolic HF distinction became popular because it was easy to use, neatly divided the HF world into 2 halves, and reflected the leading pathophysiological factor believed to cause each syndrome. However, population-based studies showed that LV diastolic dysfunction was present in a large proportion of adults without HF, and that patients with “systolic HF” were even more likely to have diastolic dysfunction compared to patients with so-called “diastolic HF.”
Thus entered the term HF with normal systolic function (HFNSF)—a term that did not make assumptions regarding underlying disease mechanisms and could therefore accommodate emerging evidence of pathophysiological processes extending beyond diastolic dysfunction to vascular, atrial, pulmonary, right-sided, and noncardiovascular organ (e.g., renal) dysfunction. However, HFNSF was deemed suboptimal when it became apparent that systolic function was not necessarily normal in these patients, and that myocardial contractile dysfunction existed despite normal overall chamber pump function.
The term HF with normal EF (HFNEF) was then embraced and adopted in guidelines. However, EF is a continuous variable with a normal distribution within the population, and the threshold value to define “normal” versus “reduced” EF is arbitrary. Indeed, Framingham Heart Study participants with an EF of 40% to 50% were at greater risk of HF and death compared with those with an EF >50% (3), and distinct physiological differences were described among Chinese with HF and EF >55% versus EF of 40% to 55% (4).
Furthermore, the “normal” distribution shifts in the very population most affected by this syndrome: data from MESA (the Multi-Ethnic Study of Atherosclerosis) (5) has shown that EF “normally” rises with age and is higher in women than men in the general population (Figure 1). The key issue is that EF is a fraction, which will increase as the heart remodels and the LV end-diastolic volume (denominator) shrinks out of proportion to the stroke volume (numerator). This prompts the question, what is the normal EF in an elderly female patient who has HF? If “normal” is a higher EF in these patients, then by using an age- and sex-neutral cutoff of 50% to define HFNEF, we are effectively selecting for elderly women who actually have “relatively abnormal” EF for their age and sex. By extrapolation, this concept may apply to all subjects with smaller heart sizes (smaller LV end-diastolic volumes)—not just women (versus men) or those with concentrically remodeled ventricles (elderly, hypertensive), but also subjects of smaller body size in general.
One may stop here and argue that we should not be looking at EF in the first place (1). However, the most significant counterargument to this is that clinical trials using EF to stratify HF have revealed 2 phenotypes that respond differently to the same therapy: renin-angiotensin-aldosterone system blockade improves survival in HFrEF, but not in HFNEF. Any classification that can guide treatment would be useful in clinical practice: a well-accepted example being the classification of myocardial infarction into ST-segment elevation versus non–ST-segment elevation myocardial infarction, as opposed to the outdated terminology Q-wave versus non–Q-wave myocardial infarction. Although we still have a long way to go before we understand the pathophysiological differences between HFrEF and HFNEF as deeply as we do for ST-segment elevation versus non–ST-segment elevation myocardial infarction, recent studies have been revealing and continue to demonstrate differences at the cardiac chamber and ultrastructural levels, as well as the hemodynamic response to therapeutic interventions. Until we can effectively tease apart pathophysiological subtypes in HF using a different classification system of proven utility for clinical management and targeted therapy, we are left with our current system of using EF.
Hence, the case for the term HF with preserved EF (HFpEF), which makes no assumptions regarding what a normal EF is, and arguably rolls off the tongue more easily than “HF with relatively normal EF depending on age, sex, and body size” (HFRNEFDASBS). Furthermore, the humble small p allows us to acknowledge the tongue-in-cheek nature of our arguments on semantics, with hidden emoticons as in HF:pEF. After all, regardless of favored nomenclature, we are united in our efforts to better understand, prevent, and treat this syndrome.
Please note: Dr Lam is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research grants from Boston Scientific, Medtronic, and Vifor Pharma; and has received consultancy fees from Bayer Healthcare and Novartis.
- American College of Cardiology Foundation
- Sanderson J.E.
- Wang T.J.,
- Evans J.C.,
- Benjamin E.J.,
- Levy D.,
- LeRoy E.C.,
- Vasan R.S.
- Cheng S.,
- Fernandes V.R.,
- Bluemke D.A.,
- McClelland R.L.,
- Kronmal R.A.,
- Lima J.A.