An increase of 5 or more points linked to decreased mortality

Patients may be better at assessing heart failure clinical status than physicians, according to a cohort study that compared New York Heart Association class 1-4 (NYHA I-IV), a functional measure applied by physicians, to patient-reported assessment captured by the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS).

The study, which included 2,872 chronic heart failure patients, examined the concordance between NYHA classes and KCCQ-OS scores and worsening heart failure.

“At 12 months, 1,002 patients (34.9%) had a change in NYHA class (599 [20.9%] with improvement; 403 [14.0%] with worsening) and 2,158 patients (75.1%) had a change of 5 or more points in KCCQ-OS (1388 [48.3%] with improvement; 770 [26.8%] with worsening),” wrote Stephen J. Greene, MD, of the Duke Clinical Research Institute in Durham, North Carolina, and colleagues. “The most common trajectory for NYHA class was no change (1870 [65.1%]), and the most common trajectory for KCCQ-OS was an improvement of at least 10 points (1047 [36.5%]). After adjustment, improvement in NYHA class was not associated with subsequent clinical outcomes, whereas an improvement of 5 or more points in KCCQ-OS was independently associated with decreased mortality (hazard ratio, 0.59; 95% CI, 0.44-0.80; P< .001) and mortality or HF hospitalization (hazard ratio, 0.73; 95% CI, 0.59-0.89; P = .002).”

The findings were published online in JAMA Cardiology.

The landmark analysis completed at 12 months revealed 206 deaths (7.2%), 231 HF hospitalizations (8.0%) and 398 (13.9%) HF hospitalizations or deaths.

The researchers also evaluated patient reported outcomes (PROs) using the Euro-Qol 5 dimensions (EQ-5D), a utility index “which reflects the degree of patient difficulty with mobility, self-care, usual activity, pain or discomfort, and anxiety or depression, with a maximal score of 1 designating perfect health, 0 equivalent to death, and lower than 0 worse than death.”

Greene et al demonstrated that “not only were the KCCQ results different from the NYHA, the KCCQ was actually more accurate in estimating outcome,” wrote Paul A. Heidenreich, MD, MS, of the VA Palo Alto Health Care System and the Department of Medicine, Stanford University School of Medicine, in an editorial published with the paper. “While this finding should not be interpreted to mean that NYHA class has no prognostic value, the result indicates that the KCCQ was more sensitive to changes associated with prognosis. The discordance between patient-and clinician-reported outcomes was greater for women, patients with lower income, and individuals with chronic obstructive pulmonary disease (COPD). The COPD finding would be expected if clinicians attempted to exclude shortness of breath due to COPD from heart failure while patients did not. However, the sex and income differences suggest there may be differences in medical history taking for these patient groups that deserve further study.”

The study participants were culled from patients with reduced ejection fraction heart failure (HFrEF) who were enrolled in the CHAMP-HF registry from December 2015 through October 2017. “Patients had complete NYHA class and KCCQ-OS data at baseline and 12 months.”

The median age of patients was 68, most were White (75.1%), and 30.4% were women.

Baseline characteristics:

  • The majority of patients were NYHA Class I (10.9%) or Class II (75.1%).
  • Almost half of the patients had KCCQ-OS scores ranging from 75 to 100, indicating “best health status.”
  • A third of patients had KCCQ-OS scores ranging from 50-74, indicating mild disease.
  • At baseline, 52% of patients had mild discordance between NYHA class and KCCQ-OS scores and 10.2 had moderate discordance, while 37.8% of the patients had concordance between NYHA class and KCCQ-OS.
  • A majority (75.2%) of participants had EQ-5D indices that were discordant with NYHA class.

“At baseline, among patients with discordance between NYHA class and KCCQ-OS, most had worse NYHA class (1222 of 1787 [68.4%]) rather than worse KCCQ-OS (565 of 1787 [31.6%]),” Greene et al wrote.

Older patients were likely to have worse baseline NYHA class than KCCQ-OS score. Conversely, “being a woman or of Hispanic ethnicity and having higher BMI, chronic obstructive pulmonary disease, and coronary artery disease were each associated with a lower likelihood of worse NYHA class than KCCQ-OS,” they added. “At 12 months, age and Hispanic ethnicity continued to be associated with the likelihood of NYHA class being worse than KCCQ-OS, with addition of higher left ventricular ejection fraction associated with lower likelihood of NYHA class–KCCQ-OS category discordance.”

Factors associated with KCCQ-OS being worse than NYHA class at baseline including lower income and heart rate higher than 65 beats per minute. “At 12 months, lower household income, chronic obstructive pulmonary disease, diabetes, and being a woman were associated with higher risk of discordance, and no factors were associated with lower risk of discordance,” Greene et al wrote.

The researchers said that “uptake of PRO measures within HF care has been slow and varied, even though they have been recommended as measures of quality,” and Heidenreich acknowledged this issue in his editorial.

’The PRO result should be made available to the clinician before meeting with the patient to help guide patient discussions. Any discrepancy between symptoms reported during the visit and symptoms reported on the PRO form can be addressed. The implication of the study by Greene et al is that the NYHA class should be reconsidered if it does not match the patient reported data. When used together, prognosis assessment and treatment decisions will be improved,” Heidenreich wrote.

Greene and colleagues listed a number of limitations to their analysis, including the fact that “no clear range of KCCQ scores matches the 4 NYHA classes, in part because of the variability in assigning NYHA class.” As a result, they selected “a priori, 4 equally sized 25-point ranges of PROs …” Additionally, there may have been a selection bias, since the patients had all agreed to participate in the CHAMP-HF registry. Finally, survival bias “may have contributed to NYHA class and KCCQ-OS generally showing more improvement than worsening over time.”

  1. During outpatient follow-up of 12 months in this cohort study, 75% of 2,872 patients had a clinically meaningful change in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) of 5 or more points, and a KCCQ improvement of 5 or more points was independently associated with decreased mortality.

  2. Compared with the clinician-assigned NYHA class, the patient-reported KCCQ-OS appears to be more likely to detect meaningful change in health status over time, and changes in KCCQ-OS may have more prognostic value than changes in NYHA class.

Peggy Peck, Editor-in-Chief, BreakingMED™

This analysis and the CHAMP-HF registry were funded by Novartis Pharmaceuticals Corporation.

Greene reported receiving research support from the American Heart Association; Amgen; AstraZeneca;Bristol Myers Squibb; Merck & Co; the National Heart, Lung, and Blood Institute (NHLBI); and Novartis and receiving personal fees from Amgen, Cytokinetics, and Merck & Co.

Heidenreich reported no disclosures.

Cat ID: 3

Topic ID: 74,3,730,3,192,925