Abstract Background Classification of chronic heart failure (HF) is on the basis of criteria that may not adequately capture disease heterogeneity. Improved phenotyping may help inform research and ...therapeutic strategies. Objectives This study used cluster analysis to explore clinical phenotypes in chronic HF patients. Methods A cluster analysis was performed on 45 baseline clinical variables from 1,619 participants in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) study, which evaluated exercise training versus usual care in chronic systolic HF. An association between identified clusters and clinical outcomes was assessed using Cox proportional hazards modeling. Differential associations between clinical outcomes and exercise testing were examined using interaction testing. Results Four clusters were identified (ranging from 248 to 773 patients in each), in which patients varied considerably among measures of age, sex, race, symptoms, comorbidities, HF etiology, socioeconomic status, quality of life, cardiopulmonary exercise testing parameters, and biomarker levels. Differential associations were observed for hospitalization and mortality risks between and within clusters. Compared with cluster 1, risk of all-cause mortality and/or all-cause hospitalization ranged from 0.65 (95% confidence interval 95% CI: 0.54 to 0.78) for cluster 4 to 1.02 (95% CI: 0.87 to 1.19) for cluster 3. However, for all-cause mortality, cluster 3 had a disproportionately lower risk of 0.61 (95% CI: 0.44 to 0.86). Evidence suggested differential effects of exercise treatment on changes in peak oxygen consumption and clinical outcomes between clusters (p for interaction <0.04). Conclusions Cluster analysis of clinical variables identified 4 distinct phenotypes of chronic HF. Our findings underscore the high degree of disease heterogeneity that exists within chronic HF patients and the need for improved phenotyping of the syndrome. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437 )
...of its activities, the committee has reduced the documentation burden on clinicians and hospitals in the hope that this will thereby allow them to focus on more critical areas of quality ...measurement and improvement. ...the performance measures were extended to assess functional outcomes. Valid, reliable, disease-specific patient-reported questionnaires include the Kansas City Cardiomyopathy Questionnaire (KCCQ); Minnesota Living with Heart Failure Questionnaire (MLHFQ); and Chronic Heart Failure Questionnaire (CHFQ).2Patient symptoms have demonstrated clinically important deterioration since last assessment.3A documented plan of care may include >=1 of the following: reevaluation of medical therapy, including uptitration of doses, consideration of electrical device therapy, recommended lifestyle modifications (e.g., salt restriction, exercise training), initiation of palliative care, referral for more advanced therapies (e.g., transplant, ventricular assist device), or referral to disease management programs.4Counseling should be specific to each individual patient and include documentation of a discussion regarding the risk of sudden and nonsudden death AND the efficacy, safety, and risks of an ICD.
To identify patients at increased risk for cardiovascular outcomes, apparent treatment resistant hypertension (aTRH) is defined as having a blood pressure (BP) above goal despite the use of ≥3 ...antihypertensive therapies of different classes at maximally tolerated doses, ideally including a diuretic. In light of growing scientific interest in the treatment of this group, a multistakeholder think tank was convened to discuss the current state of knowledge, improve the care of these patients, and identify appropriate study populations for future observational and randomized trials in the field. Although recent epidemiologic studies in selected populations estimate that the prevalence of aTRH is 10% to 15% of hypertensive patients, further large-scale observational studies will be needed to better elucidate risk factors. To spur the development of therapies for aTRH, the development of an “aTRH” label for pharmacologic and device therapies with a developmental pathway including treatment added to the use of existing therapies is favored. Although demonstration of adequate BP lowering should be sufficient to gain Food and Drug Administration approval for therapies targeting aTRH, assessment of improvement in quality of life and cardiovascular outcomes is also desirable and considered in Centers for Medicare and Medicaid Services coverage decisions. Device trials under the aTRH label will need uniform and consistent processes for defining appropriate patient populations as well as postapproval registries assessing both long-term safety and duration of responses. Finally, patients with aTRH are likely to benefit from evaluation by a hypertension team to assure proper patient identification, diagnostic work-up, and therapeutic management before consideration of advanced or novel therapies to lower BP.
Background Exercise training is recommended for chronic heart failure (HF) patients to improve functional status and reduce risk of adverse outcomes. Elevated plasma levels of amino-terminal ...pro-brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and cardiac troponin T (cTnT) are associated with increased risk of adverse outcomes in this patient population. Whether exercise training leads to improvements in biomarkers and how such improvements relate to clinical outcomes are unclear. Methods and Results Amino-terminal pro-brain natriuretic peptide, hs-CRP, and cTnT levels were assessed at baseline and 3 months in a cohort of 928 subjects from the HF-ACTION study, a randomized clinical trial of exercise training versus usual care in chronic HF patients with reduced left ventricular ejection fraction (<35%). Linear and logistic regressions were used to assess 3-month biomarker levels as a function of baseline value, treatment assignment (exercise training vs usual care), and volume of exercise. Linear regression and Cox proportional hazard modeling were used to evaluate the relations between changes in biomarker levels and clinical outcomes of interest that included change in peak oxygen consumption (peak VO2 ), hospitalizations, and mortality. Exercise training was not associated with significant changes in levels of NT-proBNP ( P = .10), hs-CRP ( P = .80), or detectable cTnT levels ( P = .83) at 3 months. Controlling for baseline biomarker levels or volume of exercise did not alter these findings. Decreases in plasma concentrations of NT-proBNP, but not hs-CRP or cTnT, were associated with increases in peak VO2 ( P < .001) at 3 months and decreased risk of hospitalizations or mortality ( P ≤ .04), even after adjustment for a comprehensive set of known predictors. Conclusions Exercise training did not lead to meaningful changes in biomarkers of myocardial stress, inflammation, or necrosis in patients with chronic HF. Only improvements in NT-proBNP translated to reductions in peak VO2 and reduced risk of clinical events.
The aim of this study was to determine whether biomarkers of myocardial stress and fibrosis improve prediction of the mode of death in patients with chronic heart failure.
The 2 most common modes of ...death in patients with chronic heart failure are pump failure and sudden cardiac death. Prediction of the mode of death may facilitate treatment decisions. The relationship between amino-terminal pro-brain natriuretic peptide (NT-proBNP), galectin-3, and ST2, biomarkers that reflect different pathogenic pathways in heart failure (myocardial stress and fibrosis), and mode of death is unknown.
HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) was a randomized controlled trial of exercise training versus usual care in patients with chronic heart failure due to left ventricular systolic dysfunction (left ventricular ejection fraction ≤35%). An independent clinical events committee prospectively adjudicated mode of death. NT-proBNP, galectin-3, and ST2 levels were assessed at baseline in 813 subjects. Associations between biomarkers and mode of death were assessed using cause-specific Cox proportional hazards modeling, and interaction testing was used to measure differential associations between biomarkers and pump failure versus sudden cardiac death. Discrimination and risk reclassification metrics were used to assess the added value of galectin-3 and ST2 in predicting mode of death risk beyond a clinical model that included NT-proBNP.
After a median follow-up period of 2.5 years, there were 155 deaths: 49 from pump failure, 42 from sudden cardiac death, and 64 from other causes. Elevations in all biomarkers were associated with increased risk for both pump failure and sudden cardiac death in both adjusted and unadjusted analyses. In each case, increases in the biomarker had a stronger association with pump failure than sudden cardiac death, but this relationship was attenuated after adjustment for clinical risk factors. Clinical variables along with NT-proBNP levels were stronger predictors of pump failure (C statistic: 0.87) than sudden cardiac death (C statistic: 0.73). Addition of ST2 and galectin-3 led to improved net risk classification of 11% for sudden cardiac death, but not pump failure.
Clinical predictors along with NT-proBNP levels were strong predictors of pump failure risk, with insignificant incremental contributions of ST2 and galectin-3. Predictability of sudden cardiac death risk was less robust and enhanced by information provided by novel biomarkers.
Abstract Background Data from a cardiopulmonary exercise (CPX) test are used to determine prognosis in patients with chronic heart failure (HF). However, few published studies have simultaneously ...compared the relative prognostic strength of multiple CPX variables. Objectives The study sought to describe the strength of the association among variables measured during a CPX test and all-cause mortality in patients with HF with reduced ejection fraction (HFrEF), including the influence of sex and patient effort, as measured by respiratory exchange ratio (RER). Methods Among patients (n = 2,100, 29% women) enrolled in the HF-ACTION (HF-A Controlled Trial Investigating Outcomes of exercise traiNing) trial, 10 CPX test variables measured at baseline (e.g., peak oxygen uptake V o2 , exercise duration, percent predicted peak V o2 %ppV o2 , ventilatory efficiency) were examined. Results Over a median follow-up of 32 months, there were 357 deaths. All CPX variables, except RER, were related to all-cause mortality (all p < 0.0001). Both %ppV o2 and exercise duration were equally able to predict (Wald chi-square: ∼141) and discriminate (c-index: 0.69) mortality. Peak V o2 (ml·kg–1 ·min–1 ) was the strongest predictor of mortality among men (Wald chi-square: 129) and exercise duration among women (Wald chi-square: 41). Multivariable analyses showed that %ppV o2 , exercise duration, and peak V o2 (ml·kg–1 ·min–1 ) were similarly able to predict and discriminate mortality. In men, a 10% 1-year mortality rate corresponded to a peak V o2 of 10.9 ml·kg–1 ·min–1 versus 5.3 ml·kg–1 ·min–1 in women. Conclusions Peak V o2 , exercise duration, and % ppV o2 carried the strongest ability to predict and discriminate the likelihood of death in patients with HFrEF. The prognosis associated with a given peak V o2 differed by sex. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437 )
Patient-reported outcomes (PRO) are defined as reports coming directly from patients about how they feel or function in relation to a health condition and its therapy. Although there are numerous ...compelling reasons why PRO could be an important help in clinical care, they have not evolved into clinical tools integrated into care. The purpose of this review is to assess existing PRO instruments for heart failure with respect to their psychometric properties and potential for use in clinical care. We performed a systematic search of articles published between July 2008 and January 2015 within the MEDLINE, PROMIS, PROQOLID, and Cochrane Library databases. Included instruments had to be developed and tested for heart failure and have had their development processes and psychometric properties described. A total of 31 instruments were identified, 9 of which met all inclusion criteria. After evaluating each remaining instrument in terms of psychometric and clinical criteria and symptom coverage, only 2 instruments—Minnesota Living with Heart Failure and Kansas City Cardiomyopathy questionnaire—met all evaluation criteria. Although clinically useful PRO instruments exist, increasing education to providers on the value and interpretability of PRO instruments, as well as a more streamlined approach to their implementation in the clinical setting is necessary. A clinical trial comparing the routine use of disease-specific PRO with clinical care could further support their incorporation into practice.
Background Heart failure trials use a variety of measures of functional capacity and quality of life. Lack of formal assessments of the relationships between changes in multiple aspects of ...patient-reported health status and measures of functional capacity over time limits the ability to compare results across studies. Methods Using data from HF-ACTION (N = 2331), we used the Pearson correlation coefficients and predicted change scores from linear mixed-effects modeling to demonstrate the associations between changes in patient-reported health status measured with the EQ-5D visual analog scale and the Kansas City Cardiomyopathy Questionnaire (KCCQ) and changes in peak VO2 and 6-minute walk distance at 3 and 12 months. We examined a 5-point change in KCCQ within individuals to provide a framework for interpreting changes in these measures. Results After adjustment for baseline characteristics, correlations between changes in the visual analog scale and changes in peak VO2 and 6-minute walk distance ranged from 0.13 to 0.28, and correlations between changes in the KCCQ overall and subscale scores and changes in peak VO2 and 6-minute walk distance ranged from 0.18 to 0.34. A 5-point change in KCCQ was associated with a 2.50-mL kg−1 min−1 change in peak VO2 (95% CI 2.21-2.86) and a 112-m change in 6-minute walk distance (95% CI 96-134). Conclusions Changes in patient-reported health status are not highly correlated with changes in functional capacity. Our findings generally support the current practice of considering a 5-point change in the KCCQ within individuals to be clinically meaningful.
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