Guidelines summarize and evaluate all available evidence at the time of the writing process, on a particular issue with the aim of assisting health professionals in selecting the best management strategies for an individual patient, with a given condition, taking into account the impact on outcome, as well as the risk-benefit-ratio of particular diagnostic or therapeutic means. Guidelines and recommendations should help the health professionals to make decisions in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate.

Background —Inflammatory immune activation is an important feature in chronic heart failure (CHF). Little is known about the prognostic importance of tumor necrosis factor-α (TNF-α), soluble TNF-receptor 1 and 2 (sTNF-R1/sTNF-R2), interleukin-6 (IL-6), and soluble CD14 receptors (sCD14) in CHF patients. Methods and Results —In 152 CHF patients (age 61±1 years, New York Heart Association [NYHA] class 2.6±0.1, peak V̇ o ₂ 17.3±0.6 mL · kg ⁻¹ · min ⁻¹ , mean±SEM) plasma concentrations of immune variables were prospectively assessed. During a mean follow-up of 34 months (>12 months in all patients), 62 patients (41%) died. Cumulative mortality was 28% at 24 months. In univariate analyses, increased total and trimeric TNF-α, sTNF-R1, and sTNF-R2 (all P ≤0.0001), sCD14 ( P =0.0007), and IL-6 ( P =0.005) predicted 24-month mortality. With multivariate analysis and receiver operating characteristics, sTNF-R1 emerged among all cytokine parameters as the strongest and most accurate prognosticator in this CHF population, regardless of follow-up duration and independently of NYHA class, peak V̇ o ₂ , V̇ e /V̇ co ₂ slope, left ventricular ejection fraction, and wasting ( P <0.001). The receiver operating characteristic area under the curve for sTNF-R1 was greater than for sTNF-R2 at 6, 12, and 18 months (all P <0.05). Conclusions —sTNF-R1 was the strongest and most accurate prognosticator, independent of established markers of CHF severity. Assessment of sTNF-R1 may be useful in identifying patients who are at high risk of death and in monitoring patients undergoing anti–TNF-α treatment.

Background— Serum uric acid (UA) could be a valid prognostic marker and useful for metabolic, hemodynamic, and functional (MFH) staging in chronic heart failure (CHF). Methods and Results— For the derivation study, 112 patients with CHF (age 59±12 years, peak oxygen consumption [V̇ o ₂ ] 17±7 mL/kg per minute) were recruited. In separate studies, we validated the prognostic value of UA (n=182) and investigated the relationship between MFH score and the decision to list patients for heart transplantation (n=120). In the derivation study, the best mortality predicting UA cutoff (at 12 months) was 565 μmol/L (9.50 mg/dL) (independently of age, peak V̇ o ₂ , left ventricular ejection fraction, diuretic dose, sodium, creatinine, and urea; P <0.0001). In the validation study, UA ≥565 μmol/L predicted mortality (hazard ratio, 7.14; P <0.0001). In 16 patients (from both studies) with UA ≥565 μmol/L, left ventricular ejection fraction ≤25% and peak V̇ o ₂ ≤14 mL/kg per min (MFH score 3), 12-month survival was lowest (31%) compared with patients with 2 (64%), 1 (77%), or no (98%, P <0.0001) risk factor. In an independent study, 51% of patients with MFH score 2 and 81% of patients with MFH score 3 were listed for transplantation. The positive predictive value of not being listed for heart transplantation with an MFH score of 0 or 1 was 100%. Conclusions— High serum UA levels are a strong, independent marker of impaired prognosis in patients with moderate to severe CHF. The relationship between serum UA and survival in CHF is graded. MFH staging of patients with CHF is feasible.

A proper determination of the exercise intensity is important for the rehabilitation of patients with cardiovascular disease (CVD) since it affects the effectiveness and medical safety of exercise training. In 2013, the European Association of Preventive Cardiology (EAPC), together with the American Association of Cardiovascular and Pulmonary Rehabilitation and the Canadian Association of Cardiac Rehabilitation, published a position statement on aerobic exercise intensity assessment and prescription in cardiovascular rehabilitation (CR). Since this publication, many subsequent papers were published concerning the determination of the exercise intensity in CR, in which some controversies were revealed and some of the commonly applied concepts were further refined. Moreover, how to determine the exercise intensity during resistance training was not covered in this position paper. In light of these new findings, an update on how to determine the exercise intensity for patients with CVD is mandatory, both for aerobic and resistance exercises. In this EAPC position paper, it will be explained in detail which objective and subjective methods for CR exercise intensity determination exist for aerobic and resistance training, together with their (dis)advantages and practical applications.

Background —In patients with chronic heart failure (CHF) and preserved exercise tolerance, the value of cardiopulmonary exercise testing for risk stratification is not known. Elevated slope of ventilatory response to exercise (V̇ e /V̇ co ₂ ) predicts poor prognosis in advanced CHF. Derangement of cardiopulmonary reflexes may trigger exercise hyperpnea. We assessed the relationship between cardiopulmonary reflexes and V̇ e /V̇ co ₂ and investigated the prognostic value of V̇ e /V̇ co ₂ in CHF patients with preserved exercise tolerance. Methods and Results —Among 344 consecutive CHF patients, we identified 123 with preserved exercise capacity, defined as a peak oxygen consumption (peak V̇ o ₂ ) ≥18 mL · kg ⁻¹ · min ⁻¹ (age 56 years; left ventricular ejection fraction 28%; peak V̇ o ₂ 23.5 mL · kg ⁻¹ · min ⁻¹ ). Hypoxic and hypercapnic chemosensitivity (n=38), heart rate variability (n=34), baroreflex sensitivity (n=20), and ergoreflex activity (n=20) were also assessed. We identified 40 patients (33%) with high V̇ e /V̇ co ₂ (ie, >34.0). During follow-up (49±22 months, >3 years in all survivors), 34 patients died (3-year survival 81%). High V̇ e /V̇ co ₂ (hazard ratio 4.3, P <0.0001) but not peak V̇ o ₂ ( P =0.7) predicted mortality. In patients with high V̇ e /V̇ co ₂ , 3-year survival was 57%, compared with 93% in patients with normal V̇ e /V̇ co ₂ ( P <0.0001). Patients with high V̇ e /V̇ co ₂ demonstrated impaired reflex control, as evidenced by augmented peripheral ( P =0.01) and central ( P =0.0006) chemosensitivity, depressed low-frequency component of heart rate variability ( P <0.0001) and baroreflex sensitivity ( P =0.03), and overactive ergoreceptors ( P =0.003) compared with patients with normal V̇ e /V̇ co ₂ . Conclusions —In CHF patients with preserved exercise capacity, enhanced ventilatory response to exercise is a simple marker of a widespread derangement of cardiovascular reflex control; it predicts poor prognosis, which peak V̇ o ₂ does not.