The Prognostic Value of the Diastolic Stress Test in Patients Undergoing Treadmill Stress Echocardiography

doi:10.1016/j.echo.2019.05.021

Journal of the American Society of Echocardiography

Volume 32, Issue 10, October 2019, Pages 1298-1306

https://doi.org/10.1016/j.echo.2019.05.021 Get rights and content

Highlights

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Guidelines currently recommend diastolic stress testing based on limited data.
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Diastolic assessment (E/e’ pre- and post-exertion) can be done in most stress echoes.
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DST identifies ischemic, nonischemic positive DST, and nonischemic negative DST.
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Ischemic stress tests portend extremely poor heart failure outcomes.
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Nonischemic positive DST predict worse outcomes compared to negative DST.

Background

Exercise stress echocardiography (SE) is well validated for the evaluation of myocardial ischemia. Diastolic stress testing (DST) is recommended in the 2016 American Society of Echocardiography and European Association of Cardiovascular Imaging Guidelines for unexplained dyspnea. This study's aim was to prognostically evaluate the DST prospectively in a large stress testing population.

Methods

Patients underwent SE with mitral E/e' measured before and after maximal treadmill exertion to estimate diastolic function. Patients were divided into four groups: group 1 (n = 201)—ischemic; group 2 (n = 1,563)—negative DST (E/e'_pre < 12, E/e'_post < 12); group 3 (n = 68)—positive DST (E/e'_pre < 12, E/e'_post ≥ 12); group 4 (n = 314)—high baseline E/e' (E/e'_pre ≥ 12).

Results

Consecutive patients (n = 2,201, 770 [35%] female; 58 ± 12 years) were followed after SE for 27,964 patient-months. Time to first heart failure event (composite of heart failure admission, worsening New York Heart Association class, worsening ejection fraction, or cardiovascular death) was analyzed and adjusted using Cox proportional hazards regression. Ischemic patients hazard ratio (HR) was 28, 95% CI, 17-44, P < .0005, for subsequent heart failure compared with negative DST patients. Nonischemic, positive DSTs were highly predictive (HR = 4.2; 95% CI, 1.6-11.0; P = .001); while high E/e'_pre was not predictive (HR = 1.3; 95% CI, 0.7-2.4; P = .49) of future heart failure events.

Conclusions

DST differentiates heart failure prognosis in patients with induced diastolic dysfunction. Ischemia predictably portends the worst heart failure outcomes, and nonischemic, positive diastolic stress tests predicted more events compared with negative tests. These prognostic data support and add to the recommendations of the 2016 guidelines.

Section snippets

Methods

Consecutive patients referred to GenesisCare clinical testing facilities for SE between June 2011 and June 2014 were studied prospectively. Indications for testing were typically dyspnea or chest pain. Standard Bruce protocol treadmill testing with digital gated echocardiography before and after exercise was performed. Patients requiring dobutamine SE and those with resting left bundle branch block, a paced rhythm or atrial fibrillation, reduced ejection fractions (<50%), or mitral valve

Results

There were 2,201 consecutive SEs available with complete data for analysis from 770 female (35%), and 1,431 male patients. Mean ± SD age was 58 ± 12 years. The baseline characteristics are detailed in Table 1. Total follow-up was for 27,964 patients-months (up to 5 years per patient, for a mean of 13 ± 19 months).

Discussion

SE is a well validated investigation for the assessment of cardiac status and pathologies, especially for the detection of obstructive coronary artery disease.5, 21, 22 One of the manifestations of myocardial ischemia is abnormal relaxation and diastolic dysfunction.1, 23, 24 Diastolic abnormalities occur earlier in the ischemic cascade than systolic changes.1, 3 Assessment of diastolic parameters during exercise has been shown to be feasible and valuable.1, 5, 7, 8 In normal subjects, exertion

Conclusion

The 2016 American Society of Echocardiography and the European Association of Cardiovascular Imaging Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography Guidelines define and discuss the role of the DST. The results presented in this study generally validate the DST in a very large stress testing population. These new data suggest an expansion in the role of the DST, with minor changes to the definitions suggested in the 2016 guidelines. Measuring the

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Cited by (20)

Expanding the Utility of Exercise Echocardiography with Doppler Assessment of Left Ventricular Filling Pressure
2024, Journal of the American Society of Echocardiography
Prognostic Significance of Elevated Left Ventricular Filling Pressures with Exercise: Insights from a Cohort of 14,338 Patients
2024, Journal of the American Society of Echocardiography
Exercise echocardiography can assess for cardiovascular causes of dyspnea other than coronary artery disease. However, the prevalence and prognostic significance of elevated left ventricular (LV) filling pressures with exercise is understudied.
We evaluated 14,338 patients referred for maximal symptom-limited treadmill echocardiography. In addition to assessment of LV regional wall motion abnormalities (RWMAs), we measured patients’ early diastolic mitral inflow (E), septal mitral annulus relaxation (e’), and peak tricuspid regurgitation velocity before and immediately after exercise.
Over a mean follow-up of 3.3 ± 3.4 years, patients with E/e’ ≥15 with exercise (n = 1,323; 9.2%) had lower exercise capacity (7.3 ± 2.1 vs 9.1 ± 2.4 metabolic equivalents, P < .0001) and were more likely to have resting or inducible RWMAs (38% vs 18%, P < .0001). Approximately 6% (n = 837) had elevated LV filling pressures without RWMAs. Patients with a poststress E/e’ ≥15 had a 2.71-fold increased mortality rate (2.28-3.21, P < .0001) compared with those with poststress E/e’ ≤ 8. Those with an E/e’ of 9 to 14, while at lower risk than the E/e’ ≥15 cohort (hazard ratio [HR] = 0.58 [0.48-0.69]; P < .0001), had higher risk than if E/e’ ≤8 (HR = 1.56 [1.37-1.78], P < .0001). On multivariable analysis, adjusting for age, sex, exercise capacity, LV ejection fraction, and presence of pulmonary hypertension with stress, patients with E/e’ ≥15 had a 1.39-fold (95% CI, 1.18-1.65, P < .0001) increased risk of all-cause mortality compared with patients without elevated LV filling pressures. Compared with patients with E/e’ ≤ 15 after exercise, patients with E/e’ ≤15 at rest but elevated after exercise had a higher risk of cardiovascular death (HR = 8.99 [4.7-17.3], P < .0001).
Patients with elevated LV filling pressures are at increased risk of death, irrespective of myocardial ischemia or LV systolic dysfunction. These findings support the routine incorporation of LV filling pressure assessment, both before and immediately following stress, into the evaluation of patients referred for exercise echocardiography.
Association of Echocardiographic Parameter E/e’ With Cardiovascular Events in a Diverse Population of Inpatients and Outpatients With and Without Cardiac Diseases and Risk Factors
2023, Journal of the American Society of Echocardiography
Citation Excerpt :
The septal E/e’ ratio showed a graded mortality hazard when >9, with a markedly worse mortality profile when >14.27 In addition to the aforementioned studies, E/e’ has been shown to be associated with outcomes in patients with sepsis and chronic kidney disease, and E/e’ measured in diastolic stress test is associated with myocardial ischemia.35-37 The present study investigated the association of E/e’ with various CV events by using ICD codes.
The echocardiographic parameter E/e’ has been associated with cardiovascular (CV) events. However, few studies have analyzed multiple associated CV outcomes using E/e’ in a diverse population of both inpatients and outpatients with and without cardiac diseases and risk factors.
Medical records of 75,393 patients without atrial fibrillation (AF) with first available E/e’ were retrieved from our hospital database. Patients with mitral valve disease were excluded, and the remainder were studied in protocol 1 (70,819 patients). Patients with hypertension, diabetes mellitus, hyperlipidemia, CV diseases, prior CV events, CV surgeries, and left ventricular ejection fraction <50% or missing left ventricular ejection fraction were further excluded, and the remaining patients were studied in protocol 2 (14,665 patients). The study outcomes are major adverse CV events (MACE), which included myocardial infarction (MI), AF, ischemic and hemorrhagic stroke (IHS), hospitalization for heart failure (HHF), and cardiac death. The primary outcomes were MACE and each of the MACE components.
At the end of maximal 5-year follow-up (median 22.18 months with interquartile range 7.20-49.08 months for MACE in protocol 1 and 23.46 months with interquartile range 8.15-49.02 months for MACE in protocol 2), compared with an E/e’ value of <8, an intermediate value of E/e’ 8 to 15 and a high value of E/e’ >15 were significantly associated with MACE, MI, AF, IHS, HHF, and cardiac death in protocol 1 (all P < .0001). In protocol 2, an intermediate E/e’ value of 8 to 15 and a high value of E/e’ >15 were significantly associated with MACE, MI, AF, IHS, HHF, and CV death (all P < .05), except an intermediate value E/e’ 8 to 15 was not associated with AF.
In a diverse population of inpatients and outpatients with and without cardiac diseases and risk factors, the echocardiographic parameter E/e’ was associated with CV events and is a useful marker of risk.
Isovolumic Contraction Velocity in Heart Failure With Reduced Ejection Fraction and Effect of Sacubitril/Valsartan: the PROVE-HF Study
2023, Journal of Cardiac Failure
To assess tissue Doppler-derived mitral annular isovolumic contraction velocity (ICV) after starting sacubitril/valsartan (sac/val) for the treatment of heart failure with reduced ejection fraction (HFrEF) and left ventricular [LV] EF < 40%).
ICV may inform load-independent systolic function; combining ICV and LVEF may improve assessment of LV contractility.
Among 651 participants with HFrEF treated with sac/val, echocardiograms were performed at baseline, 6 and 12 months. Pretreatment median ICVs and LVEFs were used for classification to predict LV reverse remodeling, health status using the Kansas City Cardiomyopathy Questionnaire, and biomarker concentrations.
The mean age was 64.6 ± 12.4 years, and 28% were women, baseline LVEF: 28.9% ± 6.9%. Compared to baseline, median ICV increased post sac/val therapy (4.6 [3.5, 6.1] vs 4.9 [3.6, 6.4]; P = 0.005). ICV added value to separate and combined models of biomarkers and clinical and echocardiographic variables for prediction of post-therapy EF recovery. Classification using baseline ICV/EF yielded relatively equal numbers in 4 groups based on low/high ICV or LVEF. Most deleterious results for remodeling, health status and biomarkers were found in patients with low ICV/low EF, whereas patients with high ICV/high EF had the best profiles; other groups were intermediate. Significant shifts toward better ICV/EF profiles were noted post sac/val treatment compared to baseline, with doubling of high ICV/high EF (241 [60%] vs 123 [31%]) and 78% reduction of low ICV/low EF (28 [7%] vs 125 [32%]).
In HFrEF, ICV adds to the profiling of systolic function and represents an independent predictor of reverse cardiac remodeling after treatment with sac/val. ICV changes may be used for assessment of treatment responses.
What are the prognostic implications and factors relating to exercise induced electrocardiographic ST segment changes in the setting of a non-ischemic stress echocardiogram?
2022, International Journal of Cardiology
Citation Excerpt :
The mean age was 58 ± 12 years. There were 1087 females (36%), which was expected for this cohort [13,17,18]. During follow-up, overall event rates were low.
Electrocardiographic (ECG) changes during stress testing are a common and perplexing finding during non-ischemic stress echocardiography (niSE). Research has provided conflicting results regarding the implications.
SE was performed after maximal Bruce protocol treadmill exercise.
3020 consecutive patients, mean age 58 ± 12 years, 36% female, were followed-up for up to 9 years (mean 36 ± 21 months) post niSE. Time to first cardiac event (composite of heart failure admission, worsening New York Heart Association class, worsening ejection fraction, acute coronary syndrome, revascularization, angina or cardiovascular death) was analysed and adjusted using Cox proportional hazards regression. Prognostic significance was found with 1.5 mm of downsloping or horizontal ST depression. Adjusting for baseline differences, increased risk of composite major adverse cardiac events was shown with at least 1.5 mm of exercise induced ST depression (Hazard ratio [HR] of 2.47, 95% Confidence ratio [CI] 1.67–3.72, p < 0.0001). Patients achieving high level exercise capacity (≥13 metabolic equivalents or METs) with ST depression lower risk of cardiac events during follow-up.
Patients with ST segment depression but non-ischemic stress imaging have a poorer prognosis compared to patients with niSE with normal stress ECGs. ST depression of 1.5 mm or more was established as a prognostically significance value. High exercise capacity was associated with an improved prognosis, and ECG changes in that setting can be regarded as false positives. All niSE have low risk of a cardiac event in the very short term (<12 months). Overall, ST depression during non-ischaemic stress imaging is not a benign finding.
Updated knowledge and practical implementations of stress echocardiography in ischemic and non-ischemic cardiac diseases: An expert consensus of the Working Group of Echocardiography of the Hellenic Society of Cardiology
2022, Hellenic Journal of Cardiology
Citation Excerpt :
In this case, the exercise achieved parameters: average E/e’ ≥15 which may be accompanied or not by TR Vmax >3.4 m/s, have been proposed as supportive indices of HFpEF, but only after assessing resting functional and morphological echocardiographic indices and natriuretic peptides measurements. Positive DSTE is highly predictive of future HFpEF-related events (admissions, cardiovascular death, worsening NYHA Class, or worsening ejection fraction)151. Therefore, it is necessary to incorporate DSTE in a diagnostic algorithm for HFpEF or unexplained dyspnea, accompanied by a complex of echocardiographic and hemodynamic indices.
Stress echocardiography (SE) is a well established and valid technique, widely used for the diagnostic evaluation of patients with ischemic and nonischemic cardiac diseases. This statement of the Echocardiography Working Group of the Hellenic Society of Cardiology summarizes the consensus of the writing group regarding the applications of SE, based on the expertise of their members and on a critical review of present medical literature. The main objectives of the consensus document include a comprehensive review of SE methodology and training—which focus on the preparation, the protocols used, the analysis of the SE images, and updated, evidence-based knowledge about SE applications on ischemic and nonischemic heart diseases, such as in cardiomyopathies, heart failure, and valvular heart disease.

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: Conflicts of Interest: None.

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2019 by the American Society of Echocardiography.

Clinical InvestigationStress EchocardiographyThe Prognostic Value of the Diastolic Stress Test in Patients Undergoing Treadmill Stress Echocardiography

Highlights

Background

Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

Conclusion

J Am Soc Echocardiogr

Am J Cardiol

Int J Cardiol

J Am Coll Cardiol

J Am Soc Echocardiogr

J Am Coll Cardiol

Int J Cardiol

Heart Lung Circ

J Am Soc Echocardiogr

J Am Soc Echocardiogr

J Am Coll Cardiol

Heart Lung Circ

Am Heart J

Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging

J Am Soc Echocardiogr

Clinical Investigation
Stress Echocardiography
The Prognostic Value of the Diastolic Stress Test in Patients Undergoing Treadmill Stress Echocardiography