By Van Selby, MD
Assistant Professor of Medicine, University of California, San Francisco, Cardiology Division, Advanced Heart Failure Section
Dr. Selby reports no financial relationships relevant to this field of study.
SYNOPSIS: Adding echocardiographic assessment of diastolic function during exercise improves the accuracy of current algorithms for evaluating suspected heart failure with preserved ejection fraction.
SOURCE: Obokata M, Kane GC, Reddy YN, et al. Role of diastolic stress testing in the evaluation for heart failure with preserved ejection fraction: A simultaneous invasive-echocardiographic study. Circulation 2017;135:825-838.
Confirming a diagnosis of heart failure with preserved ejection fraction (HFpEF) can be challenging when classic signs are not present. Algorithms from major societies often recommend including natriuretic peptide levels and data from resting echocardiography to evaluate suspected HFpEF. However, the accuracy of these algorithms has not been evaluated rigorously. Furthermore, many patients who present with HFpEF only demonstrate hemodynamic abnormalities during exercise, and, therefore, incorporating exercise echocardiography may increase sensitivity.
The authors studied consecutive patients referred to the Mayo Clinic catheterization laboratory for simultaneous exercise right heart catheterization (RHC) and echocardiography to evaluate exertional dyspnea of unclear etiology. All patients exhibited left ventricular ejection fraction (EF) ≥ 50%. Patients were diagnosed with HFpEF based on the combination of clinical symptoms and elevated pulmonary capillary wedge pressure (PCWP), either at rest (> 15 mmHg) or with cycle ergometer exercise (≥ 25 mmHg). Patients with normal PCWP and no other clear hemodynamic abnormality were diagnosed with non-cardiac dyspnea (NCD).
Of 74 patients who completed the study, 24 (32%) were found to have NCD and 50 (68%) met criteria for HFpEF based on invasive data. Among patients with confirmed HFpEF, 18% had an N-Terminal pro-B-type natriuretic peptide (NT-proBNP) < 125 pg/mL, the level most frequently used to rule out HFpEF. Using guideline-recommended algorithms based on rest echocardiography alone, only 60% of subjects with confirmed HFpEF met diagnostic criteria, demonstrating poor sensitivity.
All patients were then reclassified after including exercise echocardiographic data. Patients were classified as HFpEF if the average ratio of transmitral E to mitral annular e’ velocities (E/e’) at peak exercise was > 14 lateral or the septal E/e’ > 15. Using this added criteria, the sensitivity increased to 90%, although the false positive rate also was higher at 29%.
The authors concluded that algorithms based solely on echocardiographic assessment of diastolic function at rest are not sensitive for diagnosing HFpEF in patients with unexplained dyspnea, and including measurement of exercise E/e’ improves diagnostic accuracy.
COMMENTARY
When clear signs and symptoms of heart failure are not present, right heart catheterization with exercise is considered the gold standard for diagnosing HFpEF in patients with unexplained dyspnea. The majority of patients with suspected HFpEF are not referred for invasive testing, so guidelines for the diagnosis of HFpEF generally require evidence of elevated left ventricular filling pressure as measured by either echocardiography (i.e., an elevated E/e’ ratio) or natriuretic peptide levels.
The authors conducted an important study that highlights the limitations of noninvasive testing performed at rest only. Depending on the exact algorithm used, 40-66% of all patients who met invasive criteria for HFpEF would not have been diagnosed based on resting echocardiography alone. This is explained partly by the fact that 44% of subjects who met invasive criteria for HFpEF actually demonstrated PCWP < 15 at rest. Therefore, the problem with relying on the E/e’ ratio at rest is not inaccuracy, but rather the fact that it misses exercise-induced abnormalities.
Although sensitivity of current algorithms was poor, this study confirmed the specificity of standard echocardiographic criteria for diagnosis of diastolic dysfunction and HFpEF. Patients with high E/e’ at rest are likely to exhibit elevated PCWP at rest as well, and in these cases, exercise testing often is unnecessary. It is patients who present with suspected HFpEF but normal E/e’ at rest in whom exercise echocardiography should be considered. Also, it is worth noting that natriuretic peptide levels, often used in the evaluation of suspected heart failure, were normal in 18% of patients with HFpEF.
Exercise echocardiography can be technically challenging. This was a single-center study with all echocardiograms performed in a highly experienced research laboratory. Even in this setting, many of the echocardiographic studies were technically limited. E/e’ only could be obtained in 80% of subjects at peak exercise, and the tricuspid regurgitant velocity only could be measured in 50% of subjects at peak exercise.
The specific diagnostic algorithm proposed by the authors will require prospective validation before it can be recommended widely. However, the argument that exercise often is required for a thorough evaluation of suspected HFpEF is valid and should encourage practitioners to use exercise testing more frequently in the evaluation of dyspnea of unclear etiology. Exercise echocardiography may be particularly well-suited for patients with an intermediate pre-test probability of HFpEF in whom adequate echocardiographic windows can be obtained. In patients with normal diastolic function on resting echocardiography and an average E/e’ at peak exercise < 14 lateral and septal E/e’ < 15, a diagnosis of HFpEF is unlikely. It is important to remember that including exercise improves sensitivity, but also increases the false positive rate. Therefore, patients with abnormal E/e’ may require exercise RHC to confirm the diagnosis.
Adding echocardiographic assessment of diastolic function during exercise improves the accuracy of current algorithms for evaluating suspected heart failure with preserved ejection fraction.
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