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NYHA class I NYHA class II NYHA class III NYHA class IV No physical limitations Slight limitation of physical activity Marked limitation of physical activity Symptoms at rest Stage A Stage B Stage C Stage D Patients at risk for heart failure
No structural diseaseStructural disease
No heart failure symptomsStructural disease
Heart failure symptomsEnd-stage disease NYHA = New York Heart Association
Reprinted from Okwuosa IS, Princewill O, Nwabueze C, et al. The ABCs of managing systolic heart failure: past, present, and future. Cleve Clin J Med 2016; 83(10):753-765. doi:10.3949/ccjm.83a.16006
Patient group Classa At risk of heart failure BNP or NT-proBNP for prevention IIa Ambulatory with new-onset dyspnea BNP or NT-proBNP for diagnosis I With NYHA class II-IV symptoms BNP or NT-proBNP for prognosis I Other biomarkers of myocardial injury or fibrosisb for prognosis IIb With acute dyspnea in the emergency department BNP or NT-proBNP for diagnosis I BNP or NT-proBNP, and cardiac troponin for prognosis I Hospitalized for acute decompensated heart failure BNP or NT-proBNP, and cardiac troponin for prognosis I BNP or NT-proBNP before discharge for prognosis IIa Other biomarkers of myocardial injury or fibrosisb for prognosis IIb Recommendation Classa Aldosterone receptor antagonistsb IIb Angiotensin II receptor blockers IIb Routine use of nitrates or phosphodiesterase-5 inhibitors is ineffective III ↵a Class of recommendation (I strong, Ila moderate, Ilb weak, III no benefit).
↵b In patients with ejection fraction ≥ 45%, elevated B-type natriuretic peptide levels or heart failure admission within 1 year, estimated glomerular filtration rate > 30 mL/ min, creatinine < 2.5 mg/dL, potassium < 5.0 mmol/L.
Information from reference 1.
Patient group Classa With hypertension at increased risk < 130/80 mm Hg should be the optimal blood pressure I With heart failure with reduced ejection fraction Guideline-directed medical treatment titrated to attain a blood pressure of < 130/80 mm Hg I Nondihydropyridine calcium channel blockers not recommended III With heart failure with preserved ejection fraction and symptoms of volume overload Diuretics to control hypertension I With heart failure with preserved ejection fraction and persistent hypertension after management of volume overload Guideline-directed medical therapy titrated to attain systolic blood pressure < 130 mm Hg. Although there are limited data to guide the choice of antihypertensive therapy in HFpEF, preferred agents include RAAS inhibition with ACE-I, ARB, and mineralocorticoid receptor antagonists (spironolactone). I Nitrates not recommended in HFpEF, unless given for symptomatic coronary artery disease, due to association with a signal of harm or decreased exercise tolerance. III ↵a Class of recommendation (I strong, III no benefit).
ACE-I = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; HFpEF = heart failure with preserved ejection fraction; RAAS = renin-angiotensin-aldosterone system
Information from reference 1.
SERVE-HF54 (Treatment of Sleep-Disordered Breathing With Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients With Heart Failure) Aim: To determine whether adaptive servo-ventilation, a form of noninvasive ventilation that automatically adjusts to give the right amount of inspiratory pressure support upon inhalation, vs standard therapy alone could decrease morbidity and mortality in heart failure with reduced ejection fraction and predominantly central sleep apnea as was suggested by a post hoc analysis of a previous trial.52 Design: Multicenter, single-blind randomized controlled trial, N = 1,325 Primary end point: Composite end point of time to event for death from any cause, lifesaving cardiovascular intervention (transplant, left ventricular assist device, defibrillation), or unplanned hospitalization for heart failure over 5 years. Findings: Not only was there no significant change in the primary end point, the treatment arm actually showed a significant increase in cardiovascular (hazard ratio 1.34, P= .0006) and all-cause (hazard ratio 1.28, P= .01) mortality. One prominent but hotly debated hypothesis is that the Cheyne-Stokes respirations in central sleep apnea are compensatory in severe heart failure, perhaps allowing the pulmonary musculature to rest, attenuating sympathetic nervous system activity, and avoiding acidosis due to hypercapnia. SAVE56 (Sleep Apnea Cardiovascular Endpoints) Aim: To determine whether continuous positive airway pressure (CPAP) plus standard therapy vs standard therapy alone would decrease cardiovascular events in patients with moderate to severe obstructive sleep apnea and known coronary or cerebrovascular disease. Design: Multicenter, randomized controlled trial, N = 2,717 Primary end point: Composite end point of death from cardiovascular cause, myocardial infarction, stroke, or hospitalization for unstable angina, heart failure, or transient ischemic attack over nearly 4 years. Secondary end points: Cardiovascular secondary end points included the individual components of the primary composite end point, other composites of cardiovascular events, revascularization procedures, new-onset atrial fibrillation, new-onset diabetes mellitus, and death from any cause. Noncardiovascular end points included daytime sleepiness, snoring, mood (depression, anxiety), and quality-of-life scores. Findings: Contrary to prior observational studies and despite a marked improvement in apneic-hypopneic events with CPAP (29/hour to 3.7/hour), no significant difference in the primary composite end point (17% vs 15.4%, P= .34) or cardiovascular secondary end points was evident. Significant improvement was seen in the noncardiovascular secondary end points such as daytime sleepiness, snoring, mood (depression, anxiety), and quality-of-life scores. Patient group Classa With New York Heart Association (NYHA) class II-IV heart failure and suspicion of sleep-disordered breathing or excessive daytime sleepiness A formal sleep assessment to distinguish obstructive vs central sleep apnea is reasonable IIa With cardiovascular disease and obstructive sleep apnea Continuous positive airway pressure may be reasonable to improve sleep apnea and reduce daytime sleepiness IIb With NYHA class II-IV heart failure with reduced ejection fraction and central sleep apnea Adaptive servo-ventilation causes harm III ↵a Class of recommendation (IIa moderate, IIb weak, III harm).
Information from reference 1.
FAIR-HF271 (Intravenous Iron in Patients With Systolic Heart Failure and Iron Deficiency to Improve Morbidity and Mortality)
Estimated completion: October 2020AFFIRM-AHF72 (Study to Compare Ferric Carboxymaltose With Placebo in Patients With Acute Heart Failure and Iron Deficiency)
Estimated completion: June 2019HEART-FID73 (Randomized Placebo-controlled Trial of FCM as Treatment for Heart Failure With Iron Deficiency)
Estimated completion: January 2021IRONMAN74 (Effectiveness of intravenous iron treatment vs standard care in patients with heart failure and iron deficiency)
Estimated completion: February 2021