Diastolic function and its association with diabetes, hypertension and age in an outpatient population with normal stress echocardiography findings.

BACKGROUND: Diastolic dysfunction can be caused by hypertension or diabetes mellitus, and it is also often found with increasing age. In a given patient, the cause of diastolic dysfunction is therefore not always obvious. We sought to study the interplay of these risk factors for diastolic dysfunction in an outpatient population with a low likelihood of ischemic heart disease. METHODS: Consecutive patients referred for stress echocardiography were included retrospectively. Exclusion criteria included pathological stress response, atrial arrhythmia, left ventricular ejection fraction < 55%, and more than mild valvular disease. Standard diastolic parameters were recorded in all patients. In a subset of patients, mechanistic analysis of early filling was performed using the parameterized diastolic filling (PDF) method. RESULTS: We included 726 patients (median [interquartile range] age 56 (44-65) years, 57% male). The prevalence of diabetes and hypertension was 43 and 49%, respectively. In multiple linear regression modeling, the presence of diabetes, hypertension, sex and increasing age explained a moderate amount of the variance in e' velocities, E/A ratio and E/e' (R2 = 0.31-0.48, p < 0.001), and a low amount of the variance in left atrial volume index (LAVI) and the PDF parameters (n = 446, R2 = 0.05-0.17, p < 0.001). Sex was only related to LAVI and E/e' for the conventional parameters (beta - 0.94, p = 0.04, and beta - 0.91, p < 0.001, respectively). CONCLUSIONS: Diabetes, hypertension, increasing age, and to a lesser extent sex, explain a moderate amount of the variance in conventional diastolic parameters related to myocardial tissue velocities and E/A ratio in a healthy outpatient population. The effect of these risk factors was substantially less pronounced on left atrial volume index and the PDF parameters.

Mechanistic validation of the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging Guidelines for the assessment of diastolic dysfunction in heart failure with reduced ejection fraction.

BACKGROUND: The American Society for Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) 2016 guidelines for assessment of diastolic dysfunction (DD) are based primarily on the effects of diastolic dysfunction on left ventricular filling hemodynamics. However, these measures do not provide quantifiable mechanistic information about diastolic function. The Parameterized Diastolic Filling (PDF) formalism is a validated theoretical framework that describes DD in terms of the physical properties of left ventricular filling. AIMS: We hypothesized that PDF analysis can provide mechanistic insight into the mechanical properties governing higher grade DD. METHODS: Patients referred for echocardiography showing reduced left ventricular ejection fraction (< 45%) were prospectively classified into DD grade according to 2016 ASE/EACVI guidelines. Serial E-waves acquired during free breathing using pulsed wave Doppler of transmitral blood flow were analyzed using the PDF formalism. RESULTS: Higher DD grade (grade 2 or 3, n = 20 vs grade 1, n = 30) was associated with increased chamber stiffness (261 ± 71 vs 169 ± 61 g/s2, p < 0.001), increased filling energy (2.0 ± 0.9 vs 1.0 ± 0.5 mJ, p < 0.001) and greater peak forces resisting filling (median [interquartile range], 18 [15-24] vs 11 [8-14] mN, p < 0.001). DD grade was unrelated to chamber viscoelasticity (21 ± 4 vs 20 ± 6 g/s, p = 0.32). Stiffness was inversely correlated with ejection fraction (r = - 0.39, p = 0.005). CONCLUSIONS: Higher grade DD was associated with changes in the mechanical properties that determine the physics of poorer left ventricular filling. These findings provide mechanistic insight into, and independent validation of the appropriateness of the 2016 guidelines for assessment of DD.

Normal Reference Values for Assessing Diastolic Function Using the Parameterized Diastolic Filling Formalism Method in Patients with Normal Results of Rest and Stress Echocardiography.

The parameterized diastolic filling (PDF) method can be used to study the mechanics of early diastolic left ventricular (LV) filling. However, there are no publications describing the reference ranges of the PDF parameters. This study retrospectively recruited patients with normal results on rest and stress echocardiography and no diabetes or hypertension (n=138, 45% female). DICOM images of the resting E-wave from transmitral pulsed wave Doppler flow velocities were analyzed using freely available software. Viscoelastic energy loss (c) and stiffness (k) were higher in males compared to females (p≤0.001 for both). There were no correlations between any of the PDF parameters and age (p>0.05 for all). In males, stiffness was correlated with systolic blood pressure (r=0.24, p=0.04), and load and filling energy were correlated with diastolic blood pressure (r=-0.27, p=0.02, and r=-0.29, p=0.01, respectively). Sex-specific normal 95% reference limits for PDF analysis of early LV filling are presented for clinical use.

Cardiac Amyloidosis Shows Decreased Diastolic Function as Assessed by Echocardiographic Parameterized Diastolic Filling.

Cardiac amyloidosis is a rare but serious condition with poor survival. One of the early findings by echocardiography is impaired diastolic function, even before the development of cardiac symptoms. Early diagnosis is important, permitting initiation of treatment aimed at improving survival. The parameterized diastolic filling (PDF) formalism entails describing the left ventricular filling pattern during early diastole using the mathematical equation for the motion of a damped harmonic oscillator. We hypothesized that echocardiographic PDF analysis could detect differences in diastolic function between patients with amyloidosis and controls. Pulsed-wave Doppler echocardiography of transmitral flow was measured in 13 patients with amyloid heart disease and 13 age- and gender matched controls. E- waves (2 to 3 per subject) were analyzed using in-house developed software. Nine PDF-derived parameters were obtained in addition to conventional echocardiographic parameters of diastolic function. Compared to controls, cardiac amyloidosis patients had a larger left atrial area (23.7 ± 7.5 cm2 vs. 18.5 ± 4.8 cm2, p = 0.04), greater interventricular septum wall thickness (14.4 ± 2.6 mm vs. 9.3 ± 1.3 mm, p < 0.001), lower e' (0.06 ± 0.02 m/s vs. 0.09 ± 0.02 m/s, p < 0.001) and higher E/e' (18.0 ± 12.9 vs. 7.7 ± 1.3, p = 0.001). The PDF parameter peak resistive force was greater in cardiac amyloidosis patients compared to controls (17.9 ± 5.7 mN vs. 13.1 ± 3.1 mN, p = 0.03), and other PDF parameters did not differ. PDF analysis revealed that patients with cardiac amyloidosis had a greater peak resistive force compared to controls, consistent with a greater degree of diastolic dysfunction. PDF analysis may be useful in characterizing diastolic function in amyloid heart disease.

Kinematic analysis of diastolic function using the freely available software Echo E-waves - feasibility and reproducibility.

BACKGROUND: Early diastolic left ventricular (LV) filling can be accurately described using the same methods used in classical mechanics to describe the motion of a loaded spring as it recoils, a validated method also referred to as the Parameterized Diastolic Filling (PDF) formalism. With this method, each E-wave recorded by pulsed wave (PW) Doppler can be mathematically described in terms of three constants: LV stiffness (k), viscoelasticity (c), and load (x 0). Also, additional parameters of physiological and diagnostic interest can be derived. An efficient software application for PDF analysis has not been available. We aim to describe the structure, feasibility, time efficiency and intra-and interobserver variability for use of such a solution, implemented in Echo E-waves, a freely available software application ( www.echoewaves.org ). RESULTS: An application was developed, with the ability to open DICOM files from different vendors, as well as rapid semi-automatic analysis and export of results. E-waves from 20 patients were analyzed by two investigators. Analysis time for a median of 34 (interquartile range (IQR) 29-42) E-waves per patient (representing 63 %, IQR 56-79 % of the recorded E-waves per patient) was 4.3 min (IQR 4.0-4.6 min). Intra-and intraobserver variability was good or excellent for 12 out of 14 parameters (coefficient of variation 2.5-18.7 %, intraclass correlation coefficient 0.80-0.99). CONCLUSION: Kinematic analysis of diastolic function using the PDF method for Doppler echocardiography implemented in freely available semiautomatic software is highly feasible, time efficient, and has good to excellent intra-and interobserver variability.