POCUS for Diastolic Dysfunction: A Review of the Literature

Abstract Emergency and critical care physicians frequently encounter patients presenting with dyspnea and normal left ventricular systolic function who may benefit from early diastolic evaluation to determine acute patient management. The current American Society of Echocardiography Guidelines approach to diastolic evaluation is often impractical for point of care ultrasound (POCUS) evaluation, and few studies have evaluated the potential use of a simplified approach. This article reviews the literature on the use of a simplified diastolic evaluation to assist in determining acute patient management.


Introduction
Symptomatic heart failure continues to have a significant associated morbidity and mortality [1]. A portion of patients hospitalized for symptomatic heart failure will be found to have preserved left ventricular systolic function (HFpEF) [2]. There are various causes of HFpEF, but most commonly patients will be diagnosed with diastolic dysfunction [1].
In 2016, the American Society of Echocardiography (ASE) and the European Association of Cardiovascular Imaging (EACI) published guidelines for the evaluation of diastolic dysfunction using echocardiography [3]. These guidelines are based on expert consensus and recommend multiple 2D and Doppler measurements to help diagnose diastolic dysfunction within the correct clinical context. Many physicians have found it impractical in the emergency department and critical care setting to collect all measurements included in the ASE guidelines at the bedside. This difficulty may be due to multiple factors [4]. For example, if the patient has hypoxemia or dyspnea, they may be unable to lay flat or be properly positioned for the sonographer to obtain an adequate apical 4 chamber view. Furthermore, many emergency physicians do not have the advanced training in echocardiography to perform these measurements.
In this article, we review the literature for evaluation of diastolic dysfunction using a simplified echocardiographic approach.

Methods
We reviewed the literature to look for simplified approaches to evaluating diastolic dysfunction using echocardiography. We identified articles through a systematic search of the Medline (PubMed) and EMBase databases for relevant articles published after September 1, 2016. Our search terms were 'diastolic heart failure'/exp OR 'diastolic function'/exp) AND ('transthoracic echocardiography'/exp OR 'point of care ultrasound'/exp) for EMBase and (("Heart Failure, Diastolic"[Mesh] OR "Diastole/ physiology"[Mesh]) AND ("Echocardiography"[Mesh] OR "Ultrasonography"[Mesh])) for PubMed.

Results
We identified 1345 studies satisfying the search terms ( Figure 1). We excluded 21 duplicate studies and 1314 irrelevant studies. We excluded studies using transesophageal echocardiography, 3D echocardiography or volumetric strain echocardiography measurements. We also excluded studies which included patients with decreased left ventricular ejection fraction, Review Abstract Emergency and critical care physicians frequently encounter patients presenting with dyspnea and normal left ventricular systolic function who may benefit from early diastolic evaluation to determine acute patient management. The current American Society of Echocardiography Guidelines approach to diastolic evaluation is often impractical for point of care ultrasound (POCUS) evaluation, and few studies have evaluated the potential use of a simplified approach. This article reviews the literature on the use of a simplified diastolic evaluation to assist in determining acute patient management. pediatrics, congenital or valvular heart disease. Lastly, we excluded review articles, posters, and abstracts. We found five articles responsive to our initial question. In addition, we found seven articles which discussed echocardiographic identifiers of mortality rather than diagnostic signs of diastolic dysfunction. The authors felt this was important to the overall topic and should be included in this report.
The characteristics of the included studies are summarized in Table 1 and Table 2. Most of the studies used retrospective data. Seven studies enrolled inpatients and three enrolled outpatient clinic patients. The sonographers for these studies were usually not identified in the reports, but we assumed they were certified cardiology echocardiographers with interpretation by a cardiologist if not otherwise stated. Most of the studies did not reference the 2016 ASE guidelines or compare the data directly to these guidelines.

Discussion
Recognizing echocardiographic evidence of diastolic dysfunction can be very helpful when attempting to differentiate the underlying etiology of patients presenting with dyspnea and it has also been found useful as a clinical predictor for patients with sepsis without the need for invasive measurements [4][5][6].
In 2016, the ASE and the EACI published an updated guideline for the evaluation of diastolic dysfunction. The goal of the update was to create a more simplified set of guidelines, as it was noted that the prior guidelines, published in 2009, were considered too complex and led to difficulty for providers in diagnosing diastolic dysfunction [3]. The updated guidelines review the literature and set forth steps for diagnosis based on the ejection fraction (EF) of the patient and other factors, such as concerns for constrictive or restrictive pericarditis.
For patients found to have a normal LVEF, the guidelines recommend the evaluation of four parameters: E/E' ratio, septal e' or lateral e' velocity, tricuspid regurgitation (TR) velocity and left atrial (LA) volume index. The first three values are to be obtained through the apical 4 chamber (A4C) view with pulse wave Doppler of the mitral valve flow, tissue Doppler imaging of the mitral valve septum or lateral plane, and continuous wave Doppler of the tricuspid valve. The last calculation, volumetric analysis of the left atrium, requires a volume assessment in the traditional A4C and then an additional orthogonal view from the A4C view. For diastolic dysfunction to be diagnosed, three or four of these measurements must be abnormal. If only one or none of these values is noted to be abnormal, diastolic dysfunction is excluded. If two of these values are noted to be abnormal, then the result is "indeterminate." Unlike the 2009 guidelines, the 2016 guidelines do not specify further gradation of diastolic dysfunction in patients with normal EF.
The 2016 ASE guidelines, despite simplifying the 2009 guidelines, still present challenges for a timely evaluation at bedside in the ED setting. One of the biggest challenges is that providers in the emergency department are trained in POCUS. POCUS is a limited survey seeking to answer a simple yes or no question. However, the diagnosis of diastolic dysfunction often requires more complicated parameters and measurements than what POCUS can provide involving both echogenic and clinical evaluation.    A review by Greenstein highlights the difficulties in the critical care setting, many of which also apply in the ED setting [4]. Current guidelines require the assessment of both mitral and tricuspid flow patterns, with the latter potentially difficult to obtain a crisp Doppler signal. It also requires both septal and lateral measurements of the mitral valve annular velocity without clarifying their added benefit over a single plane measurement. If these views can be obtained, they may provide a sufficient basis for a diagnosis or exclusion of diastolic dysfunction. However, if these views cannot be obtained or are not sufficient for diagnosis, then the guidelines call for obtaining potential LA volumetric assessment via two orthogonal views. This measurement can be time-consuming and is not a measurement typically performed by providers trained in POCUS. While the first view may be obtained in the A4C view to obtain this measurement, a second orthogonal view may be more difficult to obtain. Additionally, the ability to obtain an A4C view, orthogonal views, or multiple views of the same area is likely to be limited by patient positioning, presence of monitors, and other external devices. It may be impractical if not impossible to turn or reposition a critically ill patient to provide optimal evaluation. All these factors make the current diastolic function assessment by ASE guidelines impractical in the acute care setting.
In our review there was substantial heterogeneity across studies in the evaluation of diastolic dysfunction and the markers of mortality. Most of the studies looked at mitral valve Doppler velocities [7][8][9][10][11], while a few looked at left atrial volumes [12][13][14]. Four of the articles looked at the ratio of E/e' and found an associated increase in mortality with those patients who had an increase in the E/e' value [10][11]. These findings are similar to those presented in other articles published prior to the 2016 guidelines. In 2016, Lanspa et al looked at septic ICU patients and found that the E/A ratio, e' velocity and E/e' ratio were the most important in predicting 28-day mortality [15]. However, in our review of the literature, the values of E/e' and e' for diagnosing diastolic dysfunction varied among the different studies and ranged from E/e' >9 to E/e' >15 [4,7,8,11,16,17]. One article from 2018 discussed the development of a diagnostic scoring system for diagnosing HfpEF [8]. It is the only article we found that combined echocardiographic measurements with clinical variables such as body mass index, hypertension, atrial fibrillation, pulmonary hypertension, and age. The results of the study showed robust performance in their 100patient cohort [8]. Additionally, each study had varying inclusive and exclusive criteria including presence of dysrhythmia, valvular pathology, which may limit the general applicability.
Two studies directly compared a simplified method with a comprehensive method of evaluating for diastolic dysfunction [7,16]. The Ballo et al correspondence reported that their simplified method using mitral valve Doppler values had a fair concordance with the comprehensive evaluation and often underestimated the severity of diastolic dysfunction [7]. This is in contrast to Del Rios et al, which showed good agreement between emergency physicians (EPs) and cardiologists using only the average e' value [16]. This is also in contrast to Lanspa et al (written prior to 2016 and not included in our review), which showed overestimation of the severity of diastolic dysfunction using the simplified approach as compared to the 2009 guidelines [15]. Ultimately, a simplified approach to diastolic evaluation can help better risk stratify patients presenting with dyspnea. While it does not preclude the need for further evaluation of diastolic dysfunction, a simplified evaluation can provider further information within the initial evaluation and treatment.

Limitations
While a simplified diastolic analysis can provide further diagnostic information, the technique has some drawbacks.
If not properly obtained, these measurements would likely have more limited accuracy [18]. In addition, other conditions a patient may have (e.g., restrictive pericarditis, atrial fibrillation, or heart failure) can impact the accuracy of the tissue Doppler measurement if they are unrecognized, and this could lead to a false interpretation [18]. Finally, if measurements are not reviewed in the context of the clinical picture, one risks a diagnosis of non-clinically relevant diastolic dysfunction [18]. However, studies have shown that EPs are capable of identifying clinically significant diastolic dysfunction, and other studies have shown that non-cardiologist have good inter-rater reliability for the assessment of diastolic dysfunction [19][20][21][22][23][24].
The accuracy and utility of a simplified evaluation method for diastolic dysfunction likely needs further investigation and validation studies. There are a few proposals for a simplified diastolic dysfunction evaluation, but robust research in this area, including prospective trials, is lacking. Much existing research in this area is based on retrospective review of comprehensive echocardiographic examinations with parameters that are increased in patients who have been diagnosed with diastolic dysfunction. Furthermore, a few of the articles in our review proposed a simplified diagnostic approach, yet still required complex calculations for the evaluation of diastolic dysfunction.
Simplified diastolic evaluation methods do not preclude the need for a comprehensive echocardiogram or provide a definitive diagnosis, but it helps physicians target their care in a timely fashion when comprehensive echocardiography is neither feasible nor readily available.

Conflicts of Interest
The authors have no conflicts of interest to disclose.