This study confirms the findings of prior reports and provides new information on this interesting and neglected type of HF. We observed that the prognosis of patients with HF and preserved LVSF is comparable with that of patients with reduced LVSF. The predictors of adverse outcome, however, differ between the two groups.
The proportion of patients in our study who had HF and preserved LVSF was 29%, consistent with the range of 24–55% in similar studies from the USA.2,4,5,7,8,10,11,13
The proportion in the one Japanese study we know of was 35%.19
In the EuroHeart failure survey 46% of participants with a measurement of LVSF had preserved systolic function, though only 64% of patients had such a measurement.2
In our study the average age of patients with HF and preserved LVSF was 72.6 years, a little older than that of patients with reduced LVSF (mean age 70.5 years, p
0.11). Compared with patients with reduced LVSF, more patients with a preserved LVSF tended to be older than 65 years (80% v
0.093). This too is consistent with prior studies where patients with preserved LVSF were older, though in only three studies were patients as old as ours.6,7,10
Similarly, the proportion of women with preserved LVSF (62%) was comparable with previous reports.
The present report also adds new information to the growing literature on HF with preserved LVSF in a number of important ways. In earlier studies, detailed information on the prevalence and nature of co-morbid problems, such as valvar heart disease and anaemia, and their relations with outcome are not reported.2,4,6,7,9–11,14,15
Furthermore, none of these reports provided a detailed description of renal function. Surprisingly, most studies also did not provide information on cardiac anatomy (determined echocardiographically).
The few existing studies describing renal function reported serum creatinine concentration, which can be an inaccurate measure, especially in frail elderly patients. We were able to calculate eGFR of our patients by using a validated formula. The majority of patients had a significant reduction in eGFR and, interestingly, the proportions with important reductions in eGFR were comparable in the two types of HF.
We also examined the prevalence of anaemia in our cohort, in view of the new interest in this co-morbidity as an independent predictor of worse outcome and because correcting anaemia may improve symptoms and outcome. We found a high overall prevalence of anaemia in our patients. Anaemia tended to be more common in patients with preserved LVSF than in those with reduced LVSF. We know of no prior report of the frequency of anaemia in a study of patients with HF that took account of ventricular function.
The most probable explanation for the HF syndrome in patients with preserved LVSF is diastolic dysfunction. The most probable substrate for this is left ventricular hypertrophy. We identified left ventricular hypertrophy (by echocardiography) in 56% of patients with preserved LVSF compared with 29% of patients with reduced LVSF. This observation is a much larger differential than in any of the prior hospital cohort studies. These earlier studies, however, generally reported ECG left ventricular hypertrophy. We also found that left atrial enlargement is as common in patients with preserved LVSF as in those with reduced LVSF. This was despite mitral regurgitation occurring more commonly in those with reduced LVSF. Furthermore, mitral valve forward flow velocity was greater in patients with preserved LVSF. Taken together, these findings suggest that left atrial pressure may have been greater in patients with preserved LVSF than in those with reduced LVSF.
We found that patients with preserved LVSF had a similar in-hospital length of stay to those with reduced LVSF, in keeping with other European2,6
and US studies.3,20
Very few studies have described inpatient case fatality rates. Philbin and colleagues20
reported a 3% rate in patients with preserved compared with a 5% rate in those with reduced LVSF in New York State. Cohen-Solal and colleagues,6
in a national survey of French hospitals, found these rates to be 3% and 8%, respectively. Ours were 12% and 10%, respectively. In other words, all three studies show that patients with preserved LVSF have a similar short term outcome.
Longer term mortality, time to first hospital readmission for any cause or for HF, and time to the composite outcome of readmission for any reason or death were similar in our patients with preserved or with reduced LVSF. We did find that the time to first readmission for HF or death was lower in patients with preserved LVSF than in patients with reduced LVSF. Overall, these findings are in keeping with the results of some7,10,15,21,22
but not all studies2,9,11,23,24
. The differences in findings between these studies and our own may be explained by differences in the type of population studied, such as hospitalised versus ambulatory patients,15
and duration of follow up.7
Common predictors of adverse outcome in patients with preserved or reduced LVSF were age, haemoglobin, neutrophil count, the presence of valve disease, treatment with spironolactone, and plasma concentrations of sodium and urea. Although most of these prognostic markers have been previously described, this is the first report of the prevalence and prognostic importance of haemoglobin in patients with HF and preserved LVSF. Furthermore, important differences were observed between patients with reduced and patients with preserved LVSF in factors that predict outcome. For example, COPD and male sex predicted mortality in patients with preserved LVSF but not in those with reduced LVSF. We have also described for the first time a quantitative interaction of renal function with LVSF, with serum urea concentration being a much stronger predictor of death or readmission for HF in patients with preserved LVSF than in those with reduced LVSF. Our findings underline the importance of other health problems in patients with preserved LVSF and are consistent with the notion that these patients are less likely to die of a cardiac problem and more likely to die of a non-cardiovascular cause in the long term.25
Lastly, we looked at treatment. Our overall rates of use of ACE inhibitors and, especially, β blockers are much greater than in prior reports, reflecting the more contemporary nature of our study. We found higher rates of use of ACE inhibitors and spironolactone in patients with reduced LVSF than in those with preserved LVSF The differential in the use of ACE inhibitors is in keeping with previous studies and is expected. The relatively low rates of spironolactone use are also in keeping with the results of the EuroHeart failure survey.2
Compared with other studies, we observed a greater overall use of β blockers than in some earlier reports6,12,15
but a similar rate of β blocker use to that in one more contemporary North American population.7
We also found similar rates of use of β blockers in the patients with preserved and reduced LVSF. Prior findings with β blockers, according to LVSF, have been less consistent, with two studies reporting higher rates of use in patients with preserved LVSF. There was a considerably greater use of warfarin in patients with preserved LVSF, in keeping with the higher prevalence of atrial fibrillation in these patients. Atrial fibrillation is an important risk factor for HF and is an adverse prognostic marker when HF is present.26
That atrial fibrillation is more prevalent in patients with preserved LVSF suggests that it is an important co-morbid problem in these patients. Aspirin use was greater in patients with reduced LVSF, in keeping with the greater evidence of coronary heart disease in this group.
As with any study of this type there are a number of limitations. One is generic to most studies of this type: the difficulty in assuring a diagnosis of HF in patients with preserved LVSF in the absence of an ideal test for this condition. In the future natriuretic peptides may help. A second limitation is that we chose to exclude patients with a diagnosis of myocardial infarction on the basis of increased cardiac biomarkers. There has been conflicting opinion on whether patients with a primary diagnosis of myocardial infarction and secondary HF should be included in a study of HF. The issue has become even more clouded by the recognition that troponin can be increased in a minority of patients with acutely decompensated HF without a clinically recognisable myocardial infarction.
In conclusion, there were many similarities and differences between patients with preserved LVSF and those with reduced LVSF. Patients with preserved LVSF had more co-morbidity including, notably, anaemia. Both groups have a similar and greatly reduced level of renal function. Despite quite distinctly different echocardiographic findings and treatment, patients with preserved LVSF had similar long term risks of death or readmission to hospital to those with reduced LVSF. Sex, COPD, and renal function are stronger predictors of adverse outcome in patients with preserved LVSF than in patients with reduced LVSF.