Today, I link to and excerpt from the resource below:
Kittleson MM et al. 2023 ACC expert consensus decision pathway on management of heart failure with preserved ejection
fraction: A report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 2023 May;
81:1835. (https://doi.org/10.1016/j.jacc.2023.03.393) [PubMed-Abstract] [Full-Text HTML] [Full-Text PDF].
All that follows is from the above resource.
1.1. The Scope of the Problem
Despite advances in therapy, heart failure (HF) continues to be a major cause of morbidity and mortality worldwide with a lifetime risk at age 40 years of approximately 20%.2 Although the incidence of overall HF in the United States appears to be stable or even declining, the incidence of heart failure with preserved ejection fraction (HFpEF) continues to rise.3,4 HFpEF now accounts for more than 50% of cases of HF,5 with outcomes comparable to heart failure with reduced ejection fraction (HFrEF).6 HFpEF is often under-recognized and results in substantial resource utilization.
Historically, treatment options were limited to managing comorbidities; however, revolutionary advances in the past decade regarding the pathophysiology of HFpEF, improved methods of diagnosis, and insights into prognostic predictions now yield novel, effective management strategies. With recent favorable clinical trial results, there is increasing urgency for accurate diagnosis and timely implementation of guideline-directed medical therapy (GDMT). These advances motivate the creation of this ECDP to address pivotal issues pertinent to HFpEF:
How to approach a person with shortness of breath
How to overcome diagnostic dilemma and identify a need for further testing
How to rule out mimics to avoid missed diagnosis
How to manage comorbidities and address complexities in care
How to initiate and optimize GDMTs
When and why to refer to a cardiologist or HF specialist
How to improve access to care
How to recognize sex-specific differences in diagnosis and care management
3. Assumptions and Definitions
GDMT: Treatment options supported for use by clinical practice guidelines.
HF: defined as per the Universal Definition of Heart Failure7: symptoms and/or signs of HF caused by structural/functional cardiac abnormalities and at least 1 of: 1) elevated natriuretic peptides; or 2) objective evidence of cardiogenic pulmonary or systemic congestion. An HF event, including hospitalization, is defined by the criteria outlined by the 2014 ACC/AHA Key Data Elements and Definitions for Cardiovascular Endpoint Events in Clinical Trials.15
HFrEF: Clinical diagnosis of HF and LVEF ≤40%.14
HFmrEF: Clinical diagnosis of HF and LVEF 41% to 49%.14
HF with improved EF: previous LVEF ≤40% and a follow-up measurement >40%.
HFpEF: Clinical diagnosis of HF and LVEF ≥50%14 not attributable to an underlying cause such as an infiltrative cardiomyopathy, hypertrophic cardiomyopathy, valvular disease, pericardial disease, or high-output HF.
HFpEF mimics: Clinical diagnosis of HF and LVEF ≥50% with a primary noncardiac cause (kidney or liver disease) or an underlying cardiac cause (infiltrative cardiomyopathy, hypertrophic cardiomyopathy, valvular disease, pericardial disease, or high-output HF).
New York Heart Association (NYHA) functional classification:
Class I: No limitation of physical activity. Ordinary physical activity does not cause symptoms of HF.
Class II: Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in symptoms of HF.
Class III: Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes symptoms of HF.
Class IV: Unable to perform any physical activity without symptoms of HF, or symptoms of HF at rest.
4. Pathway Summary Graphic
Many individuals present first to their primary care clinicians with symptoms of dyspnea and exercise intolerance and/or signs of congestion. The primary care clinician should be aware of HFpEF in the differential diagnosis of dyspnea, exercise intolerance, and edema; order relevant testing; be able to initiate GDMT; and recognize when a cardiology referral may be useful. The role of the cardiology specialist (cardiologist or cardiology advanced practice professional) is to exclude the presence of an alternative diagnosis to explain the individual’s presentation of dyspnea, edema, and preserved EF; optimize GDMT; encourage clinical trials; and identify indications for referral to an HF specialist. The role of the HF specialist is to pursue advanced testing in case of diagnostic dilemma; manage special or unusual cardiomyopathies, a particularly important consideration for HFpEF; identify clinical trial eligibility; and assess the need and eligibility for advanced therapies, including heart transplantation. Multidisciplinary specialist collaboration for optimization of comorbidities may include collaboration with electrophysiologists, interventional cardiologists or cardiac surgeons, endocrinologists, nephrologists, and pulmonologists.
6. Diagnosis of HFpEF
6.1. The Universal Definition of HF
The symptoms and signs of HF are well summarized by the Framingham HF Diagnostic Criteria, based on data collected during the Framingham Heart Study.16 Two or more major criteria or 1 major criterion plus 2 minor criteria are strictly required to make the diagnosis. Although clinicians will rarely resort to classifying patients using these strict criteria, the collection of symptoms and signs included in the Framingham HF Diagnostic Criteria remain useful as a reference. Major criteria include orthopnea, jugular venous distension, hepatojugular reflux, rales, S3 gallop rhythm, acute pulmonary edema, and cardiomegaly. Minor criteria include dyspnea on exertion, nocturnal cough, ankle edema, tachycardia with heart rate over 120 beats per minute, hepatomegaly, and pleural effusion.
The Universal Definition of HF provides a straightforward approach for clinicians to determine if a person’s presentation is consistent with HF (Figure 2 includes HFpEF-specific considerations).7 The Universal Definition of HF requires symptoms and/or signs of HF, as outlined earlier, caused by structural/functional cardiac abnormalities and at least 1 of the following: 1) elevated natriuretic peptides; or 2) objective evidence of cardiogenic pulmonary or systemic congestion.
Figure 2. The Universal Definition of HF∗
∗The Universal Definition of HF requires symptoms and/or signs caused by structural/functional cardiac abnormalities and at least 1 of: 1) elevated natriuretic peptides; or 2) objective evidence of cardiogenic pulmonary or systemic congestion. In HFpEF, specific additional criteria include EF 50% or greater, and consideration of pitfalls as described in the assessment of natriuretic peptide levels. BMI = body mass index; BNP = B-type natriuretic peptide; HF = heart failure; HFpEF = heart failure with preserved ejection fraction; HFrEF = heart failure with reduced ejection fraction; NT-proBNP = N-terminal pro–B-type natriuretic peptide.
If a cardiac source for dyspnea and/or edema appears likely based on the history and physical examination, the next steps would include an echocardiogram to assess for structural/functional cardiac abnormalities and laboratory evaluation, including natriuretic peptides, recognizing that a substantial proportion of individuals with HFpEF have normal natriuretic peptide levels despite unequivocal invasive hemodynamic evidence of HF.17
6.2. Differential Diagnosis of Dyspnea and Edema
Although dyspnea is a common presenting symptom of HFpEF, it is imperative to consider other causes of dyspnea before assigning the diagnosis. Dyspnea, or shortness of breath, is a frequent cause of emergency visits and hospitalizations across the spectrum of age18, 19, 20 and can pose a diagnostic challenge given the multiple potential sources of symptoms.21
An approach to the differential diagnosis of dyspnea is shown in Figure 3A, organized by cardiac, pulmonary, and other sources. A similar approach can be taken to the differential diagnosis of edema (Figure 3B),22 although the first step should be to differentiate edema from lymphedema.
Lymphedema is defined as the abnormal accumulation of interstitial fluid and fibroadipose tissue resulting from injury, infection, or congenital abnormalities of the lymphatic system. A history suggestive of risk factors such as lymph node dissection is useful, and lymphedema is most commonly unilateral. A useful physical examination finding to distinguish edema from lymphedema is the Stemmer sign. A positive Stemmer sign is characterized by a thickened skin fold at the base of the second toe or second finger. The examiner’s inability to lift the skin of the affected limb compared with the contralateral limb is considered to reflect fluid accumulation due to lymphedema. However, obesity may cause a false-positive Stemmer sign.23,24 Despite being highly sensitive, patients with a negative Stemmer sign and a high clinical suspicion for lymphedema warrant referral for lymphoscintigraphy.
Figure 3. Differential Diagnosis of Dyspnea and Edema∗
∗However, other conditions can also cause these symptoms.(A) The differential diagnosis of dyspnea. (B) The differential diagnosis of edema. CCBs = nondihydropyridine calcium-channel blockers; NSAIDs = nonsteroidal anti-inflammatory drugs.
Once lymphedema has been excluded, the 2 major pathophysiologic sources of edema can be considered: increased hydrostatic pressure and decreased oncotic pressure, as summarized in Figure 3B.
When reviewing the differential diagnosis of dyspnea and edema, it is important to note the multiple potential sources. To determine if a person’s dyspnea and/or edema is from HF, the Universal Definition of HF7 as well as HFpEF diagnostic scoring systems are useful in ascertaining the diagnosis.
6.3. HFpEF Diagnostic Scoring Systems
Although the Universal Definition of HF may be useful to guide clinicians, establishing a diagnosis of HFpEF may be more difficult given that the echocardiogram may not demonstrate obvious structural or functional cardiac abnormalities and the natriuretic peptide levels may be normal, especially in individuals with obesity.
Given the lack of testing to definitively establish the diagnosis of HFpEF, the use of clinical scoring systems may be useful to aid in the diagnostic evaluation of suspected HFpEF.25, 26, 27, 28 Both the H2FPEF and HFA-PEFF algorithms use a scoring system to help determine the likelihood that HFpEF is the underlying etiology in a dyspneic person.
The H2FPEF score was derived and validated using a gold-standard reference of invasive exercise hemodynamic measurements and is the more practical system for use by clinicians (Figure 4A). The 6 components of the H2FPEF score consist of information that is readily accessible: Heavy (body mass index [BMI] >30 kg/m2), Hypertension (on 2 or more antihypertensive medications), atrial Fibrillation, Pulmonary hypertension (estimated pulmonary artery systolic pressure >35 mm Hg on Doppler echocardiography), Elder (age >60 years), Filling pressures (E/e’ >9 on Doppler echocardiography).27 A score of 6 or more is highly suggestive of HFpEF.
Figure 4. HFpEF Diagnostic Scoring Systems∗
∗(A) The H2FPEF score includes 6 clinically accessible factors. (B) HFA-PEFF includes a more involved diagnostic algorithm starting with Pretest assessment, Echocardiographic and natriuretic peptide score, Functional testing for an advanced evaluation, and Final etiology assessment. BMI = body mass index; BNP = B-type natriuretic peptide; CMR = cardiac magnetic resonance; CT = computed tomography; GLS = global longitudinal strain; HFpEF = heart failure with preserved ejection fraction; LAVI = left atrial volume index; LVMI = left ventricular mass index; NT-proBNP = N-terminal pro–B-type natriuretic peptide; PASP = pulmonary artery systolic pressure; PET = positron emission tomography; RWT = relative wall thickness; TR = tricuspid regurgitation.
The HFA-PEFF algorithm includes natriuretic peptides in its scoring system, and it is important to note the limitations of these thresholds. Natriuretic peptide levels are generally lower in individuals with HFpEF compared with those with HFrEF,29 making the role of natriuretic peptides challenging, especially in individuals with HFpEF and obesity. Despite worse hemodynamic derangements, individuals with obesity have significantly lower natriuretic peptide concentrations than those without obesity, particularly in HFpEF17,29,30; this may result in natriuretic peptide values below the diagnostic threshold for HF, even in the presence of elevated, invasively measured cardiac filling pressures,17,29,31 although correction for BMI may be performed.32 However, the H2FPEF score does not include natriuretic peptides in its scoring system, which may also be problematic, because an elevated natriuretic peptide level is one component of the Universal Definition of HF.
The Heart Failure Association of the European Society of Cardiology has suggested that a 50% reduction in natriuretic peptide cutoff values be used for the diagnosis of HF in individuals with obesity, although this approach has not been validated and is not explicitly incorporated into the HFA-PEFF algorithm.33 Ultimately, a high suspicion of HFpEF and a low threshold for further evaluation (which may include invasive hemodynamic assessment) is warranted in individuals with dyspnea and obesity before attributing all symptoms to obesity. Indeed, the presence of obesity may result in missed opportunities to identify the presence of HFpEF, and effective treatment of both diagnoses may result in considerable improvement in quality of life and reduced hospitalizations.
Another potential limitation to the HFA-PEFF algorithm is the practicality of Step F1. Diastolic stress testing and invasive hemodynamic measurements are often not feasible in routine clinical practice. Many clinicians, when faced with the diagnostic option of diastolic stress testing or invasive hemodynamic measurements, may instead simply initiate GDMT for HFpEF (including diuretic therapy and a sodium-glucose cotransporter-2 inhibitor [SGLT2i], outlined in Section 7.1) to assess for symptomatic improvement. A therapeutic trial of GDMT is a reasonable first step instead of more intensive testing to establish a HFpEF diagnosis if the latter is not readily available.
6.4. HFpEF Mimics