Background Despite the growing epidemic of heart failure with preserved ejection fraction (HFpEF), no valid measure of patients’ health status (symptoms, function and quality of life) exists. We evaluated the Kansas City Cardiomyopathy Questionnaire (KCCQ), a validated measure of heart failure with reduced ejection fraction (HFrEF), in HFpEF patients. Methods and Results Using a prospective HF registry, we dichotomized patients into HFrEF (EF ≤ 40) and HFpEF (EF ≥ 50). The associations between NYHA class, a commonly used criterion standard, and KCCQ Overall Summary and Total Symptom domains were evaluated using Spearman correlations and two-way ANOVA with differences between HFrEF and HFpEF patients tested with interaction terms. Predictive validity of the KCCQ Overall Summary scores was assessed with Kaplan-Meier curves for death and all-cause hospitalization. Covariate adjustment was made using Cox proportional hazards models. Internal reliability was assessed with Cronbach’s α. Conclusions Among 849 patients, 200 (24%) had HFpEF. KCCQ summary scores were strongly associated with NYHA class in both HFpEF (r = −0.62, p < .001) and HFrEF patients (r = −0.55; p=0.27 for interaction). One-year event-free rates by KCCQ category among HFpEF patients were 0–25=13.8%, 26–50=59.1%, 51–75=73.8%, and 76–100=77.8%, (log rank p < .001), with no significant interaction by EF (p=0.37). The KCCQ domains demonstrated high internal consistency among HFpEF patients (Cronbach’s α = 0.96 for overall summary and ≥ 0.69 in all sub-domains). Conclusion Among patients with HFpEF, the KCCQ appears to be a valid and reliable measure of health status and offers excellent prognostic ability. Future studies should extend and replicate our findings, including the establishment of its responsiveness to clinical change.

Aims Heart failure (HF) patients with a mid-range LVEF (HFmrEF) are not well characterized. Accordingly, we examined the epidemiology, pathophysiology and clinical outcomes of HF patients with an LV EF of 40–50%. Methods and Results We identified patients with an LVEF between 40–50% at enrollment into a HF registry, and determined whether LVEF was improved, worsened, or the same compared to a prior LVEF. Three subgroups of HFmrEF patients were identified: HFmrEF improved (prior LVEF < 40%); HFmrEF deteriorated (prior LVEF > 50%); HFmrEF unchanged (prior LVEF 40–50%). The majority of patients (73%) were HFmrEF improved, 17% were HFmrEF deteriorated and 10% were HFmrEF unhanged. The demographics of the HFmrEF cohort were heterogeneous, with more CAD in the HFmrEF improved group and a more hypertension and diastolic dysfunction in the HFmrEF deteriorated group. HFmrEF improved patients had significantly (p < 0.001) better clinical outcomes relative to matched patients with HFrEF, and significantly (P < 0.01) improved clinical outcomes relative to HFmrEF deteriorated patients, whereas clinical outcomes of the HFmrEF deteriorated subgroup of patients were not significantly different from matched HFpEF patients. Conclusions Patients with a mid-range EF are heterogeneous. Obtaining historical information with regard to prior LVEF allows one to identify a distinct pathophysiological substrate and clinical course for HFmrEF patients. Viewed together, these results suggest that in the modern era of HF therapeutics, the use of LVEF to categorize the pathophysiology of HF may be misleading, and argue for establishing a new taxonomy for classifying HF patients.

Patient reported outcome measures (PROMs) are relevant independent outcomes in heart failure (HF) care and are predictive of subsequent hospitalization and death in HF. The Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Minnesota Living with Heart Failure Questionnaire (MLHFQ) are the 2 most widely adopted PROMs specific to HF. We compared their prognostic abilities in a prospective cohort of HF patients. A prospective cohort of subjects from a single-center registry was analyzed with regard to baseline KCCQ and MLHFQ scores and the outcomes of death, transplant, or left ventricular assist device implantation and hospitalization. A total of 516 subjects with reduced left ventricular ejection fraction (HFrEF) and 151 subjects with preserved left ventricular ejection fraction (HFpEF) were included. Discrimination was assessed using c-statistics based on time-to-event analyses and receiver-operator curves. The additive contribution of MLHFQ was assessed through the change in c-statistic, incremental discrimination index, and category free net reclassification index. Overall, KCCQ was superior to MLHFQ for predicting death/transplant/VAD (c-statistic 0.702 (0.666-0.738) and 0.658 (0.621-0.695) respectively, p-value for difference <0.001) and hospitalization (c-statistic 0.640 (0.613-0.666) and 0.624 (0.597-0.651), respectively, p-value for difference 0.022). However, this difference was statistically non-significant in the HFpEF group alone. When analyzing the additional prognostic information afforded by adding MLHFQ to KCCQ in the overall, HFrEF, and HFpEF groups there was no significant improvement, although adding KCCQ to MLHFQ did significantly improve risk stratification. Scoring based upon the abbreviated KCCQ-12 did not reduce the prognostic accuracy of KCCQ. In conclusion, KCCQ is more prognostic of death/ transplant/LVAD and hospitalization than MLHFQ in a combined cohort of patients with HFrEF and HFpEF, although the effect in HFpEF was less pronounced. KCCQ should be the preferred PROM for patients with HF if prognostication is a desired goal of using the PROMs.

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