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Frequently Asked Questions

Frequently Asked Questions

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    1. What is the prevalence of heart failure in the US?
    • From 2017 to 2020, an estimated 6.7 million Americans aged ≥20 years had heart failure (HF).1      
    • The prevalence of HF is expected to rise to 8.5 million Americans by 2030.2
    • Approximately 1 in 4 Americans will develop HF in their lifetime.2
    • If HF prevalence remains constant by age, the percentage of the US population with HF is projected to increase from 2.4% in 2012 to 3% in 2030.2
    2. What are the risk factors and causes for heart failure?
    • Hypertension, obesity, prediabetes, diabetes, and atherosclerotic cardiovascular disease (ASCVD) are known risk factors with high relative risk for the development of HF.3    
    • The most common causes of HF include ischemic heart disease and myocardial infarction, hypertension, and valvular heart disease.3
    • Other causes can include cardiomyopathies (familial or genetic); amyloidosis; cardiotoxicity (with cancer or other treatments); substance abuse, such as alcohol, cocaine, or methamphetamine; tachycardia, right ventricular pacing, or stress-induced cardiomyopathies; peripartum cardiomyopathy; myocarditis; autoimmune causes; sarcoidosis; iron overload (including hemochromatosis); thyroid disease; and other endocrine metabolic and nutritional causes.3
    3. How is heart failure defined?
    • According to the American College of Cardiology (ACC) and American Heart Association (AHA), HF is defined as a complex clinical syndrome with symptoms and signs that result from any structural or functional impairment of ventricular filling or ejection of blood.3
    • However, this definition of HF does not cover asymptomatic stages with structural heart disease or cardiomyopathies, which are instead considered at-risk for HF or pre-HF.3
    4. What are the symptoms and signs of heart failure?
    • Typical symptoms of HF include breathlessness; orthopnea; paroxysmal nocturnal dyspnea; reduced exercise tolerance; fatigue, tiredness, and increased time to recover after exercise; and ankle swelling.4    
    • Typical signs of HF include elevated jugular venous pressure, hepatojugular reflux, third heart sound (gallop rhythm), and laterally displaced apical impulse.4
    5. What stages of heart failure are there?
    • The ACC and AHA define 4 stages of HF, and they are meant to emphasize the development and progression of disease. Therapeutic interventions, depending on stage, aim to modify risk factors; treat risk and structural disease to prevent HF; and reduce symptoms, morbidity, and mortality.3  
    • The 4 stages are as follows3:
      • Stage A: At risk for HF
        • Patients at risk for HF but without current or previous symptoms/signs of HF and without structural or functional heart disease, or cardiac biomarkers of stretch or injury (eg, patients with hypertension, ASCVD, diabetes, metabolic syndrome and obesity, exposure to cardiotoxic agents, genetic variant for cardiomyopathy, or positive family history of cardiomyopathy)3
      • Stage B: Pre-HF
        • Patients without current or previous symptoms/signs of HF but evidence of one of the following: structural heart disease, including reduced left or right ventricular function (reduced ejection fraction [EF] or reduced strain), ventricular hypertrophy, chamber enlargement, wall motion abnormalities, or valvular heart disease; evidence of increased filling pressures (by invasive hemodynamic measurements or by noninvasive imaging suggesting elevated filling pressures); risk factors and increased levels of B-type natriuretic peptides (BNPs) or persistently elevated cardiac troponin in the absence of competing diagnoses resulting in such biomarker elevations3
      • Stage C: Symptomatic HF
        • Patients with structural heart disease with current or previous symptoms of HF3
      • Stage D: Advanced HF
        • Patients with marked HF symptoms that interfere with daily life and with recurrent hospitalizations despite attempts to optimize guideline-directed medical therapy3
    6. How do you classify symptoms and functional capacity of patients with heart failure?
    • The New York Heart Association classification provides a way of characterizing the extent of a patient’s HF based on their symptoms and functional capacity.3,5
    • It is a subjective assessment made by a clinician and can change over time; additionally, it is widely used to determine eligibility of patients for treatment strategies.3
    • It classifies patients with symptomatic HF (stage C) or advanced HF (stage D) into 1 of 4 categories.3,5 The 4 classes are as follows:
      • Class I: No symptoms and no limitation in ordinary physical activity (eg, shortness of breath when walking, climbing stairs)
      • Class II: Mild symptoms (mild shortness of breath and/or angina) and slight limitation in ordinary physical activity
      • Class III: Marked limitation in physical activity due to symptoms, even during less-than-ordinary physical activity (eg, walking short distances of 20 to 100 meters). Comfortable only at rest
      • Class IV: Severe limitations in physical activity. Experiences symptoms of HF at rest. Mostly bedbound patients
    7. How do you classify the types of heart failure by LVEF?
    • The type of HF can be classified according to a patient’s left ventricular EF (LVEF).3  
    • Classification of HF by LVEF is important due to differing prognosis and treatment response. The types of HF according to LVEF by the ACC and AHA are as follows3:  
      • HF with reduced EF (HFrEF)
        • LVEF ≤40%
      • HF with improved EF (HFimpEF)
        • Previous LVEF ≤40% and a follow-up measurement of LVEF >40%
      • HF with mildly reduced EF (HFmrEF)
        • LVEF 41%-49%
        • Evidence of spontaneous or provokable increased left ventricular filling pressures (eg, elevated natriuretic peptide, noninvasive and invasive hemodynamic measurement)
      • HF with preserved EF (HFpEF)
        • LVEF ≥50%
        • Evidence of spontaneous or provokable increased left ventricular filling pressures (eg, elevated natriuretic peptide, noninvasive and invasive hemodynamic measurement)
    • In patients with HFmrEF, 1 EF measurement at 1 time point may not be adequate as these patients usually have a dynamic trajectory to improvement from HFrEF or deterioration to HFrEF.3    
    • Serial echocardiograms to assess changes in EF, structural remodeling, and valvular function are not recommended routinely in stable patients.3
    8. What biomarkers are measured for patients with heart failure?
    • BNP and N-terminal prohormone of BNP (NT-proBNP) are 2 biomarkers frequently used to establish the presence and severity of HF.3
    • The 2022 AHA/ACC/Heart Failure Society of America (HFSA) guideline recommends that either BNP or NT-proBNP levels can be measured3:
      • In patients presenting with dyspnea to support a diagnosis or exclusion of HF (alongside clinical judgement) (COR 1, LOE A)
      • In patients with chronic HF for risk stratification (COR 1, LOE A)
      • In patients hospitalized with HF (at admission) to establish prognosis (COR1, LOE A)
      • In patients hospitalized with HF (predischarge) to inform trajectory and establish a post-discharge prognosis (COR 2a, LOE B-NR)
    9. How do you diagnose heart failure, particularly HFpEF?
    • The 2022 AHA/ACC/HFSA guideline provides a diagnostic algorithm for patients with suspected HF.3
    • In patients with suspected HF, an assessment of the patient’s clinical history, physical examination, and labs should be performed.3
      • For patients presenting with HF, the specific cause of HF should be explored using additional laboratory testing for appropriate management (COR1, LOE B-NR).3
      • The laboratory evaluation should include a complete blood count, urinalysis, serum electrolytes (including sodium, potassium, calcium, and magnesium), blood urea nitrogen, serum creatinine, glucose, fasting lipid profile, liver function tests, iron studies (serum iron, ferritin, transferrin saturation), and thyroid-stimulating hormone.3
      • For all patients presenting with HF, a 12-lead electrocardiogram (ECG) should be performed at initial encounter to optimize management (COR 1, LOE C-EO).3
      • In patients with suspected or new-onset HF, or those presenting with acute decompensated HF, a chest x-ray should be performed to assess heart size and pulmonary congestion and to detect alternative cardiac, pulmonary, and other diseases that may cause or contribute to the patient’s symptoms (COR 1, LOE C-LD).3
    • Following this assessment, natriuretic peptides (BNP/NT-proBNP) should be measured, and/or a transthoracic echocardiogram (TTE) should be performed.3
      • If natriuretic peptides are measured, an NT-proBNP >125 pg/mL or BNP ≥35 pg/mL should lead to a TTE.3
      • Additional testing should be performed if necessary.3
    • Following the TTE, an HF diagnosis should be confirmed. The cause should be determined, and the patient’s type of HF should be classified depending on their LVEF.3
    • The criteria for diagnosis of HFmrEF and HFpEF requires evidence of increased left ventricular filling pressures at rest, exercise, or other provocations. The criteria can be fulfilled with findings of elevated levels of natriuretic peptides, echocardiographic diastolic parameters (eg, E/e’ ≥15 or other evidence of elevated filling pressures), or invasive hemodynamic measurement at rest or exercise.3
    • Exercise stress testing with echocardiographic evaluation of diastolic parameters can be helpful if the diagnosis remains uncertain.3
    • The diagnosis of HFpEF is guided by a clinical composite score called the H2FPEF score, which integrates the following predictive variables: obesity, atrial fibrillation (AF), age >60 years, treatment with ≥2 antihypertensive medications, echocardiographic E/e’ ratio >9, and echocardiographic pulmonary artery systolic pressure >35 mmHg.3
      • A weighted score based on these 6 variables is used to create a composite score ranging from 0 to 9.3
      • A score <2 and ≥6 reflects low and high likelihood, respectively, for HFpEF.3
      • A score between 2 and 5 may require further evaluation of hemodynamics with exercise echocardiogram or cardiac catheterization to confirm or negate a diagnosis of HFpEF.3
    • The 2023 ACC consensus statement for HFpEF provides another diagnostic approach to HFpEF, which focuses on evaluating the differential diagnosis of dyspnea and edema (excluding noncardiac causes), establishing diagnostic probability with the H2FPEF score, and excluding cardiac mimics (especially in those with intermediate scores) before establishing the likely diagnosis of HFpEF.6
      • In the ACC approach, patients with dyspnea and/or edema should have the universal definition of HF applied to them, after assessing for a noncardiac source.6
      • The universal definition of HF requires symptoms and/or signs caused by structural or functional cardiac abnormalities and at least 1 of the following6:
        • Elevated natriuretic peptides
          • Ambulatory: BNP ≥35 pg/mL or NT-proBNP ≥125 pg/mL
          • Hospitalized: BNP ≥100 pg/mL or NT-proBNP ≥300 pg/mL
        • Or objective evidence of cardiogenic pulmonary or systemic congestion
      • In HFpEF, specific additional criteria include an EF ≥50% and considerations in the assessment of natriuretic peptides.6
        • There are lower levels of natriuretic peptides relative to HFrEF for a given elevation in left ventricular end-diastolic pressure.6
        • Higher body mass index, which is prevalent in HFpEF, is inversely associated with natriuretic peptide levels.6
    10. How do biomarkers such as BNP and NT-proBNP predict prognosis in heart failure?
    • Higher BNP and NT-proBNP levels are associated with an increased risk of adverse short- and long-term outcomes in patients with HF, including major cardiovascular events, cardiovascular death, and all-cause mortality.3
    • Data from a systematic review involving 7 studies (5 BNP and 2 NT-proBNP) found that all studies presented at least 1 estimate of incremental value of BNP/NT-proBNP relative to the base prognostic model for predicting mortality in patients with acute decompensated HF.7
    • A review of the data from the Acute Decompensated Heart Failure National Registry, which evaluated 48,629 patients with BNP assessments from 2003 to 2004, found an elevated admission BNP level to be a significant predictor of in-hospital mortality, independent of other clinical and laboratory variables.8
    • Data from a meta-analysis of 19 studies with 12,891 participants with chronic HF found that a reduction in BNP or NT-proBNP level was associated with a reduced risk of hospital stay for HF worsening.9
    • Data from a systematic review of 104 studies of patients with chronic stable HF (16 BNP and 88 NT-proBNP) found that BNP was positively associated with all-cause mortality, HF mortality, and cardiac mortality and that NT-proBNP was positively associated with all-cause mortality, cardiovascular mortality, and morbidity outcomes.10
    11. Are there different patient phenotypes for HFpEF?
    • HFpEF represents a highly heterogeneous clinical syndrome that is affected in its development and progression by many comorbidities and may impact therapeutic progress.11
    • In 2023, the Heart Failure Association (HFA) of the European Society of Cardiology developed an algorithm to identify the most common HFpEF phenotypes and identify an evidence-based treatment strategy for each phenotype.11
    • The important phenotypes that were identified include arterial hypertension, elderly (>65 years), coronary artery disease, female sex, chronotropic incompetence, obesity, iron deficiency, sleep apnea, type 2 diabetes, chronic kidney disease (CKD), atrial function mitral regurgitation, functional tricuspid regurgitation, high heart rate (>80 bpm), pulmonary hypertension, AF, cachexia, chronic obstructive pulmonary disease (COPD), EF 50 to 55%, EF >65%, and arterial hypotension.11
    • The HFpEF patient phenotypes that were profiled and provided therapeutic considerations include type 2 diabetes, arterial hypertension, obesity, COPD, iron deficiency, ischemic heart disease, and AF.11
    12. Should kidney function be accounted for in patients with heart failure?
    • According to a position statement from the HFA in 2020, renal function evaluations should be part of every encounter physicians have with HF patients as they help (1) to better understand the underlying cardio-renal physiology; (2) to improve initiation, adaptation, or continuation of evidence-based HF therapies; (3) to stratify patients at risk of adverse outcomes; and (4) to identify the presence of systemic diseases or the coexistence of independent renal disease.12
      • Evaluation of renal function as a routine work-up in every patient diagnosed with HF should include measurement of creatinine, urea, and estimated glomerular filtration rate (eGFR). A baseline evaluation of proteinuria and albuminuria using a morning urine sample may also be considered.12
    • CKD and HF frequently coexist and share common risk factors such as diabetes or hypertension.4
    • CKD may worsen cardiovascular function, causing hypertension and vascular calcification, while HF may worsen renal function through neurohormonal and inflammatory activation, increased venous pressure, and hypoperfusion.4
    • CKD and worsening renal function both appear to be more common in HFpEF as compared with HFmrEF and HFrEF,4 as approximately half of patients with HFpEF have CKD as well.11
    • CKD is also a major independent determinant of increased mortality and morbidity in HF4 and an independent predictor of adverse outcomes in HFpEF.11
    • Additionally, renal dysfunction increases the risk of toxicities of HF therapies and impairs response to diuretics.3
    13. How does eGFR predict the risk of adverse outcomes in patients with heart failure?
    • eGFR is a measure of kidney function.13
    • Reduced eGFR (or worsening kidney function) is associated with adverse outcomes in patients with HF.14-17
      • A subanalysis of the TOPCAT clinical trial, which assessed the association between renal function and mortality and hospitalization in 3392 patients with HFpEF, found that reduced eGFR (30-59 mL/min/1.73 m2) was associated with an increased risk of all-cause death, cardiovascular death, and hospitalization for HF compared with patients with eGFR ≥60 mL/min/1.73 m2.14
      • The data from a cohort study, which evaluated 24,331 community-based adults with HF and their outcomes regarding renal function from 2005 to 2008, found that when compared with patients with an index eGFR between 60 and 89 mL/min/1.73 m2, lower eGFR was associated with an independent, graded increased risk of death from any cause and hospitalization for HF or other causes.15
      • The results from an analysis of the Get With The Guidelines – Heart Failure registry, which evaluated 365,494 patients admitted for HF from 2014 to 2019, found that lower admission eGFR categories were independently associated with in-hospital mortality across EF subgroups, and there was a marked decreased in the prescription of evidence-based medical therapy for HFrEF patients as eGFR went below 90 mL/min/1.73 m2.16
      • The results from an analysis of the prospective Chronic Renal Insufficiency Cohort (CRIC) study, which included 3939 individuals with CKD from 2003 to 2008, found that in the 3971 patients analyzed, the rates of HF hospitalization and rehospitalization were higher in patients with lower eGFR.17
        • After adjusting for demographic characteristics, the rate of HF hospitalization was higher in patients with an eGFR 30-44 and <30 vs ≥45 mL/min/1.73 m2.17
        • After adjusting for demographic characteristics, the rate of 30-day readmission for HF was higher in patients with an eGFR 30-44 and <30 vs ≥45 mL/min/1.73 m2.17
    14. How does UACR predict the risk of adverse outcomes in patients with heart failure?
    • Urine albumin-to-creatinine ratio (UACR) is a marker of kidney damage.13
    • Studies have shown that increased UACR is an independent predictor of adverse outcomes in HF.17-19
      • The results from an analysis of the prospective CRIC study, which included 3939 individuals with CKD from 2003 to 2008, found that in the 3971 patients analyzed, the rates of HF hospitalization and rehospitalization were higher in patients with increased UACR.17
        • After adjusting for demographic characteristics, the rate of HF hospitalization was higher in patients with UACR 30-299 or ≥300 vs <30 mg/g.17
        • After adjusting for demographic characteristics, the rate of 30-day readmission for HF was higher in patients with UACR 30-299 or ≥300 vs <30 mg/g.17
      • The results from an analysis of the CHARM Program, which measured UACR in 2310 patients with HF at baseline and during follow-up, found that elevated UACR was associated with an increased risk of the composite outcome of death from cardiovascular causes or admission to hospital with worsening HF even after adjustment for other prognostic variables, including renal function, diabetes, and hemoglobin A1c.18
      • Data from a study of a health maintenance organization in Israel from 2017 to 2019, which evaluated 4668 patients with HF, found that increased UACR was directly associated with decreased event-free survival from death or cardiovascular hospitalizations.19
    15. What is CKM syndrome?
    • Cardiovascular-kidney-metabolic (CKM) syndrome is defined as a health disorder attributable to connections among obesity, diabetes, CKD, and cardiovascular disease (CVD), including HF, AF, coronary heart disease, stroke, and peripheral artery disease.20
    • CKM syndrome includes those at risk for CVD due to the presence of metabolic risk factors, CKD, or both, and individuals with existing CVD that is potentially related to or complicates metabolic risk factors or CKD.20

    Reference List

    1. Tsao CW, et al. Circulation. 2023;147(8):e93-621.
    2. Bozkurt B, et al. J Card Fail. 2023;29(10):1412-1451.
    3. Heidenreich PA, et al. Circulation. 2022;145:e876-e894.
    4. McDonagh TA, et al. Eur Heart J. 2021;42(36):3599-3726.
    5. The Joint Commission. New York Heart Association (NYHA) Classification. https://manual.jointcommission.org/releases/TJC2018A/DataElem0439.html. Accessed February 14, 2024.
    6. Kittleson MM, et al. J Am Coll Cardiol. 2023;81(18):1835-1878.
    7. Santaguida PL, et al. Heart Fail Rev. 2014;19(4):507-519.
    8. Fonarow GC, et al. J Am Coll Cardiol. 2007;49(19:1943-1950.
    9. Savarese G, et al. JACC Heart Failure. 2014;2(2):148-158.
    10. Oremus M, et al. Heart Fail Rev. 2014;19(4):471-505.
    11. Anker SD, et al. Eur J Heart Fail. 2023;25(7):936-955.
    12. Mullens W, et al. Eur J Heart Fail. 2020;22(4):584-603.
    13. Kidney Disease Improving Global Outcomes. Kidney Int Suppl. 2013;3:1-150.  
    14. Chen Z, et al. Front Cardiovasc Med. 2021;26:8:643358.  
    15. Smith DH, et al. Circ Cardiovasc Qual Outcomes. 2013;6(3):333-342.
    16. Patel RB, et al. J Am Coll Cardiol. 2021;78(4):330-343.
    17. Bansal N, et al. J Am Coll Cardiol. 2019;73(21):2691-2700.
    18. Jackson CE, et al. Lancet. 2009;374(9689):543-550.
    19. Shuvy M, et al. Can J Cardiol. 2020; 36(4):527-534.
    20. Ndumele CE, at al. Circulation. 2023;148(20:1606-1635. 

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