Identifying novel phenotypes of elevated left ventricular end diastolic pressure using hierarchical clustering of features derived from electromechanical waveform data.

Introduction: Elevated left ventricular end diastolic pressure (LVEDP) is a consequence of compromised left ventricular compliance and an important measure of myocardial dysfunction. An algorithm was developed to predict elevated LVEDP utilizing electro-mechanical (EM) waveform features. We examined the hierarchical clustering of selected features developed from these EM waveforms in order to identify important patient subgroups and assess their possible prognostic significance. Materials and methods: Patients presenting with cardiovascular symptoms (N = 396) underwent EM data collection and direct LVEDP measurement by left heart catheterization. LVEDP was classified as non-elevated ( ≤ 12 mmHg) or elevated (≥25 mmHg). The 30 most contributive features to the algorithm output were extracted from EM data and input to an unsupervised hierarchical clustering algorithm. The resultant dendrogram was divided into five clusters, and patient metadata overlaid. Results: The cluster with highest LVEDP (cluster 1) was most dissimilar from the lowest LVEDP cluster (cluster 5) in both clustering and with respect to clinical characteristics. In contrast to the cluster demonstrating the highest percentage of elevated LVEDP patients, the lowest was predominantly non-elevated LVEDP, younger, lower BMI, and males with a higher rate of significant coronary artery disease (CAD). The next adjacent cluster (cluster 2) to that of the highest LVEDP (cluster 1) had the second lowest LVEDP of all clusters. Cluster 2 differed from Cluster 1 primarily based on features extracted from the electrical data, and those that quantified predictability and variability of the signal. There was a low predictability and high variability in the highest LVEDP cluster 1, and the opposite in adjacent cluster 2. Conclusion: This analysis identified subgroups of patients with varying degrees of LVEDP elevation based on waveform features. An approach to stratify movement between clusters and possible progression of myocardial dysfunction may include changes in features that differentiate clusters; specifically, reductions in electrical signal predictability and increases in variability. Identification of phenotypes of myocardial dysfunction evidenced by elevated LVEDP and knowledge of factors promoting transition to clusters with higher levels of left ventricular filling pressures could permit early risk stratification and improve patient selection for novel therapeutic interventions.

Diastolic function in patients with heart failure with preserved ejection fraction and atrial fibrillation: impact of diabetes.

INTRODUCTION: The objective of our study was to evaluate the severity of diastolic dysfunction in patients with heart failure with preserved ejection fraction (HFpEF), atrial fibrillation (AF) and type 2 diabetes mellitus (T2DM) compared to those with HFpEF and AF without DM. MATERIAL AND METHODS: This is an observational, prospective, case-control study. We selected 720 patients with heart failure consecutively admitted between March 2019-December 2020, of whom 253 patients with AF. After applying the inclusion/exclusion criteria, 105 subjects remained in the study. The patients were divided into two groups, according to the presence of T2DM: group A (39 patients with T2DM, 37.14%), group B (66 patients without T2DM, 62.85%). 2D transthoracic echocardiography was performed in all patients. The study was approved by the Ethics Committee of the hospital. Statistical analysis was performed using R software, version 4.0.2. RESULTS: Patients with HFpEF, AF, and T2DM had higher LV filling pressures compared to those without DM (OR = 5.00, 95% CI: 1.77-15.19). Moreover, patients with insulin-requiring T2DM (OR = 6.25, 95% CI: 1.50-25.98) had higher LV filling pressures than those treated with oral antidiabetic drugs (OR = 4.44, 95% CI: 1.37-15.17). We demonstrated that patients with T2DM had higher E/e' ratio (difference -2.78, P 0.0003, 95% CI: -4.24 to -1.31) and lower deceleration time (DT) (difference 23.04, P 0.0002, 95% CI: 11.10-34.97) than those without T2DM. CONCLUSIONS: Patients with HFpEF, AF and T2DM have higher LV filling pressures than those without T2DM, suggesting that the presence of T2DM leads to a more severe diastolic dysfunction.

Echocardiographic assessment of diastolic dysfunction in elderly patients with severe aortic stenosis before and after aortic valve replacement.

BACKGROUND: The 2016 guidelines of the American Society of Echocardiography (ASE) and European Association of Cardiovascular Imaging (EACVI) for evaluation of left ventricular (LV) diastolic dysfunction by Doppler flow and tissue Doppler- echocardiography do not adjust assessment of high filling pressures for patients with aortic stenosis (AS). However, most of the studies on this patient group indicate age independent specific diastolic features in AS. The aim of this study is to identify disease-specific range and distribution of diastolic functional parameters and their ability to identify high N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels as a marker for high filling pressures. METHODS: In this study, 169 patients who underwent surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) were prospectively enrolled. Resting echocardiography was performed including Doppler of the mitral inflow, pulmonary venous flow, tricuspid regurgitant flow and tissue Doppler in the mitral ring and indexed volume-estimates of the left atrium (LAVI). Echocardiography, and NT-proBNP levels were assessed before TAVR/SAVR and at two postoperative visits at 6 and 12 months. RESULTS: Pre- and postoperative values were septal e'; 5.1 ± 3.9, 5.2 ± 1.6 cm/s; lateral e' 6.3 ± 2.1; 7.7 ± 2.7 cm/s; E/e'19 ± 8; 16 ± 7 cm/s; E velocity 96 ± 32; 95 ± 32 cm/s; LAVI 39 ± 8; 36 ± 8 ml/m2, pulmonary artery pressure (PAP) 39 ± 8; 36 ± 8 mmHg, respectively. The scoring recommended by ASE/EACVI detected elevated NT pro-BNP with a specificity of 25%. Adjusting thresholds towards PAP ≥ 40 mmHg, E velocity ≥ 100 cm/s, E deceleration time < 220 ms, and E/septal e' ≥ 20 or septal e' < 5.0 cm/s increased prediction of NT-proBNP levels ≥500 ng/L with substantially improved specificity (> 85%). CONCLUSION: Diastolic echocardiographic parameters in AS indicate persistent impaired relaxation and NT-proBNP indicate elevated filling pressures in most of the patients, improving only modestly 6-12 months after TAVR and SAVR. Applying the 2016 ASE/EACVI recommendations for detection of elevated filling pressures to patients with AS, elevated NT pro-BNP levels could not be reliably detected. However, adjusting thresholds of the echocardiographic parameters increased specificities to useful diagnostic levels. TRIAL REGISTRATION: The study was prospectively approved by the regional ethical committee, REK North with the registration number: REK 2010/397-10 .

When does the E/e' index not work? The pitfalls of oversimplifying diastolic function.

Since the E/e' ratio was first described in 1997 as a noninvasive surrogate marker of mean pulmonary capillary wedge pressure, it has gained a central role in diagnostic recommendations and a supremacy in clinical use that require critical reappraisal. We review technical factors, physiological influences, and pathophysiological processes that can complicate the interpretation of E/e'. The index has been validated in certain circumstances, but its use cannot be extrapolated to other situations-such as critically ill patients or children-in which it has either been shown not to work or it has not been well validated. Meta-analyses demonstrated that E/e' is not useful for the diagnosis of HFpEF and that changes in E/e' are uninformative during diastolic stress echocardiography. A similar ratio has been applied to estimate right heart filling pressure despite insufficient evidence. As a composite index, changes in E/e' should only be interpreted with knowledge of changes in its components. Sometimes, e' alone may be as informative. Using a scoring system for diastolic function that relies on E/e', as recommended in consensus documents, leaves some patients unclassified and others in an intermediate category. Alternative methods for estimating left heart filling pressures may be more accurate, including the duration of retrograde pulmonary venous flow, or contractile deformation during atrial pump function. Using all measurements as continuous variables may demonstrate abnormal diastolic function that is missed by using the reductive index E/e' alone. With developments in diagnostic methods and clinical decision support tools, this may become easier to implement.

Assessment of left ventricular diastolic function by three-dimensional transthoracic echocardiography.

Doppler echocardiography assessment of left ventricular (LV) filling pressures at rest and during exercise is the most widely used imaging technique to assess LV diastolic function in clinical practice. However, a sizable number of patients evaluated for suspected LV diastolic function show an inconsistency between the various parameters included in the flowchart recommended by current Doppler echocardiography guidelines and results in an undetermined LV diastolic function. Current three-dimensional echocardiography technology allows obtaining accurate measurements of the left atrial volumes and functions that have been shown to improve the diagnostic accuracy and prognostic value of the algorithms recommended for assessing both LV diastolic dysfunction and heart failure with preserved ejection fraction. Moreover, current software packages used to quantify LV size and function provide also volume-time curves showing the dynamic LV volume change throughout the cardiac cycle. Examining the diastolic part of these curves allows the measurement of several indices of LV filling that have been reported to be useful to differentiate patients with normal LV diastolic function from patients with different degrees of diastolic dysfunction. Finally, several software packages allow to obtain also myocardial deformation parameters from the three-dimensional datasets of both the left atrium and the LV providing additional functional parameters that may be useful to improve the diagnostic yield of three-dimensional echocardiography for the LV diastolic dysfunction. This review summarizes the current applications of three-dimensional echocardiography to assess LV diastolic function.

Diastolic function assessment by echocardiography: A practical manual for clinical use and future applications.

Diastole is an important component of the cardiac cycle, during which time optimum filling of the ventricle determines physiological stroke volume ejected in the succeeding systole. Many factors contribute to optimum ventricular filling including venous return, left atrial filling from the pulmonary circulation, and emptying into the left ventricle. Left ventricular filling is also impacted by the cavity emptying function and also its synchronous function which may suppress early diastolic filling in severe cases of dyssynchrony. Sub-optimum LA emptying increases cavity pressure, causes enlarged left atrium, unstable myocardial function, and hence atrial arrhythmia, even atrial fibrillation. Patients with clear signs of raised left atrial pressure are usually symptomatic with exertional breathlessness. Doppler echocardiography is an ideal noninvasive investigation for diagnosing raised left atrial pressure as well as following treatment for heart failure. Spectral Doppler based increased E/A, shortened E-wave deceleration time, increased E/e', and prolonged atrial flow reversal in the pulmonary veins are all signs of raised left atrial pressure. Left atrial reduced myocardial strain is another correlate of raised cavity pressure (>15 mm Hg). In patients with inconclusive signs of raised left atrial pressure at rest, exercise/stress echocardiography or simply passive leg lifting should identify those with stiff left ventricular which suffers raised filling pressures with increased venous return.

Practical Impact of New Diastolic Recommendations on Noninvasive Estimation of Left Ventricular Diastolic Function and Filling Pressures.

BACKGROUND: In 2016, an update of the 2009 recommendations for the evaluation of left ventricular (LV) diastolic function (DF) was released by the American Society of Echocardiography and the European Association of Cardiovascular Imaging. The aims of this study were to assess the concordance between the 2016 and 2009 recommendations and to test the impact of the consideration of "myocardial disease" recommended in the 2016 update on the evaluation of diastolic dysfunction (DD) and LV filling pressures in patients with normal and reduced LV ejection fractions referred to a general echocardiography laboratory. METHODS: A total of 1,508 outpatients referred to an echocardiography laboratory during a predefined 5-month period were prospectively enrolled. All patients underwent targeted clinical history and Doppler echocardiographic examination. DD and LV filling pressures were assessed according to 2009 and 2016 recommendations. Concordance was calculated using the κ coefficient and overall proportion of agreement. RESULTS: Overall proportion of agreement between the two recommendations was 64.7% (κ = 0.43). Comparing the 2009 and 2016 recommendations, 47.5% and 36.1% patients, respectively, had DD (P < .0001), and 22.7% and 12.6% had elevated LV filling pressures (P < .0001). This difference remained significant in the setting of patients with normal LV ejection fractions (21.6% vs 10.7%, P < .0001). In the application of the 2016 recommendations, whether or not the presence of "myocardial disease" was considered, the prevalence of indeterminate diastolic function was, respectively, 7.3% versus 13.7%, while patients in whom the DD grade could not be determined were 8.1% versus 14.4% (P < .0001 for all). CONCLUSIONS: Considering the presence of myocardial disease when applying the 2016 recommendations resulted in a lower prevalence of inconclusive diagnosis.

E/e` ratio is superior to speckle tracking for detecting elevated left ventricular end-diastolic pressure in patients with coronary artery disease and preserved ejection fraction.

BACKGROUND: A weak correlation has been reported between left ventricular filling pressures and the traditional echocardiographic tools for the evaluation of diastolic function in patients with coronary artery disease (CAD) and preserved left ventricular ejection fraction (LVEF). On the other hand, studies that compared invasive measurements with speckle tracking echocardiography have shown promising results, but they were not exclusively targeted on this specific population. METHODS AND RESULTS: Immediately before the left heart catheterization, a comprehensive two-dimensional Doppler echocardiography and speckle tracking analysis was prospectively performed in outpatients referred for coronary angiography. Left ventricular end-diastolic pressure (LVEDP) was measured before any contrast exposure. Eighty-one patients with coronary artery disease were studied, and the group with high LVEDP (n = 40) showed increased left atrial volume index (22 ± 6 mL/m2 vs 26 ± 8.26 mL/m2 , P = 0.04), E-wave velocity (65 ± 15 cm/s vs 78 ± 20 cm/s, P = 0.02), E/e` (average) ratio (8.14 ± 2.0 vs 11.54 ± 2.7, P = 0.03), and E/global circumferential strain rate E peak ratio (E/GCSRE ) (39 cm vs 46 cm, P < 0.01). There was a positive correlation between LVEDP and E/e` (ρ = 0.56; P = 0.03), and between LVEDP and E/GCSRE ratio (ρ = 0.43; P < 0.01). The area under the receiver operating characteristics (ROC) curve was 0.83 and 0.73, respectively (P < 0.05). E/e` and E/GCSRE were both independent predictors of elevated LVEDP (P < 0.05), with a higher C-statistic for the model including E/e` (0.89 vs 0.85). CONCLUSION: The E/e` ratio was able to identify elevated LVEDP in CAD patients with preserved LVEF with more accuracy than the E/GCSRE ratio.

Echocardiographic evaluation of left ventricular filling pressures in patients with pulmonary hypertension.

Echocardiographic assessment of diastolic dysfunction depends on surrogate parameters. In recent years, guideline committees attempted to combine these parameters to diagnostic flowcharts allowing for correct classification of left ventricular filling pressures (LVFP). The value of these diagnostic tools is limited if the applied surrogate parameters are elevated due to other reasons as is the case with maximal tricuspid regurgitation velocity. We aimed to compare the accuracy of the 2009 and the 2016 guideline recommendations in patients with pulmonary hypertension (PH). We included 101 consecutive patients who underwent right heart catheterization and transthoracic echocardiography for suspicion of PH. For the final analysis, only patients with PH were considered. The 2009 and 2016 recommendations for the assessment of diastolic function by echocardiography were applied on each patient. A total of 63 PH patients were included in the final analysis, 43% had elevated LVFP. By using the 2009 recommendations, sensitivity for correct classification of diastolic dysfunction was 67%, specificity was 82%, area under the curve (AUC) was 0.74. By using the 2016 recommendations, sensitivity for correct classification of diastolic dysfunction was 84%, specificity was 80%, AUC was 0.82. In ROC comparison, the AUC for the 2016 recommendations with 0.82 was significantly better compared to the AUC of 0.74 for the 2009 recommendations (p = 0.04). Our study demonstrates that the 2016 recommendations for echocardiographic evaluation of diastolic function are superior to the 2009 recommendations in estimating left ventricular filling pressures in patients with PH.

Indexing peak rapid filling velocity to both relaxation and filling volume to estimate left ventricular filling pressures.

AIMS: The peak transmitral velocity/peak mitral annular velocity (E/e') ratio has been used as a left ventricular (LV) filling pressure (LVFP) correlate. However, the E/e' and its changes with haemodynamic alterations have not always correlated with changes in LVFP's. We hypothesized that indexing E/e' to a measure of LV filling volume may enhance the correlation with LVFP and LVFP changes. METHODS AND RESULTS: We summarized previously obtained haemodynamic and Doppler echo data in 137 dogs with coronary microsphere embolization induced-chronic LV dysfunction prior to and following haemodynamic induced alterations in LVFP's. E/e' values were obtained as E*tau where tau is the inverse logarithmic LV pressure decay. E*tau was indexed to LV filling volume by dividing by the diastolic time velocity integral (DVI) and correlated with LV mean diastolic pressure (LVmDP). Similarly, the relationship of E/e' and E/e'/DVI to LV pre A wave pressure was evaluated in 84 patients by invasive haemodynamics and Doppler echo. Combining data from all interventions, LVmDP correlated with E*tau (r = 0.408) but more strongly with E*tau/DVI (r = 0.667, z = 3.03, P = 0.0008). The change in LVmDP correlated with the change in E*tau/DVI (r = 0.742) more strongly than E*Tau (r = 0.187, Z = 4.01, P < 0.0001). In the patient cohort, E/e' was modestly correlated with LV pre A wave pressure (r = 0.301) but more strongly correlated with E/e'/DVI (r = 0.636, z = 2.36, P = 0.0161). CONCLUSION: Indexing E to both LV relaxation and filling volume results in a more robust relation with LVFP's and with LVFP changes.

Left ventricular diastolic abnormalities other than valvular heart disease in antiphospholipid syndrome: An echocardiographic study.

BACKGROUND: Antiphospholipid syndrome (APS) can be primary or secondary to other autoimmune disorders. Besides valvular heart disease (VHD) and coronary artery disease (CAD), little is known about the impact of APS on left ventricular (LV) function. METHODS: After excluding CAD, relevant VHD and heart failure, 69 patients (mean age = 43.9 years, 40 with primary and 29 with secondary APS) were assessed by echo-Doppler. Sixty-nine heathy controls, matched for age and sex, formed the control group. APS was diagnosed in presence of at least one clinical criteria and one confirmed laboratory criteria, including lupus anticoagulant (LA) titre. The adjusted global APS score (aGAPSS), derived from the combination of risk factors for thrombosis and autoimmune-antibody profile was calculated. RESULTS: Patients had similar blood pressure and heart rate, but higher body mass index (BMI) than controls. LV mass index (p = 0.007) and left atrial volume index (p < 0.01) were greater, while early diastolic velocity (e') was lower (p = 0.003) and E/e' higher (p = 0.007) in APS. Primary APS patients had lower E/A and e' compared to both controls and secondary APS, while E/e' was higher in secondary APS than in controls. APS patients with diastolic dysfunction were older but did not differ for risk factors prevalence from those with normal/indeterminate diastolic function. In the pooled APS, LA positivity was independently associated with e' and E/e' after adjusting for age, BMI and aGAPSS in separate multivariate models. CONCLUSION: In APS, LV diastolic abnormalities are detectable. They are more pronounced in primary APS and independently associated with LA positivity.

A Comparison of the Strain and Tissue Doppler-Based Indices as Echocardiographic Correlates of the Left Ventricular Filling Pressures.

OBJECTIVES: Diastolic strain and strain rate, combined with E (peak transmitral velocity), have been proposed as novel noninvasive predictors of left ventricle (LV) filling pressures, avoiding angulation errors inherent to tissue Doppler indices (TDI). The primary objective was to study the correlation of strain-based indices (SBI) and TDI with pulmonary artery catheter-derived LV end-diastolic pressures (LVEDP). The secondary aim was to determine appropriate cut-off of indices to predict LVEDP ≥15 mmHg. DESIGN: A prospective observational clinical study. SETTING: Single university hospital. PARTICIPANTS: One hundred twenty adults with preserved ejection fraction (EF) undergoing coronary artery bypass grafting. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two-dimensional speckle-tracking echocardiography estimated global longitudinal diastolic strain (Ds) and strain rate (DSr) at peak mitral filling to compute E/Ds and E/10DSr. TDI was measured as the ratio of E and e' (mitral annular diastolic velocity). E/e', E/Ds, and E/10DSr were significantly higher (p < 0.001) in patients with LVEDP ≥15 mm Hg (31/120). Correlation of E/Ds, E/10DSr with LVEDP was R = 0.86 and 0.88 (p < 0.001), respectively, compared with a correlation of R = 0.63 (p < 0.001) for E/e'. SBI correlated well with LVEDP ≥15 mm Hg compared with TDI. E/Ds ≥11 and E/10DSr ≥12 had higher sensitivity and specificity (96.77%, 93.26%; 100%, 96.63%, respectively; area under the curve [AUC] = 0.99) than E/e'≥13 (74%,75%; AUC = 0.84) for prediction of LVEDP ≥15 mmHg. SBI accurately predicted elevated LVEDP in the indeterminate zone of 8

Precision Phenotyping in Heart Failure and Pattern Clustering of Ultrasound Data for the Assessment of Diastolic Dysfunction.

OBJECTIVES: The aim of this study was to investigate whether cluster analysis of left atrial and left ventricular (LV) mechanical deformation parameters provide sufficient information for Doppler-independent assessment of LV diastolic function. BACKGROUND: Medical imaging produces substantial phenotyping data, and superior computational analyses could allow automated classification of repetitive patterns into patient groups with similar behavior. METHODS: The authors performed a cluster analysis and developed a model of LV diastolic function from an initial exploratory cohort of 130 patients that was subsequently tested in a prospective cohort of 44 patients undergoing cardiac catheterization. Patients in both study groups had standard echocardiographic examination with Doppler-derived assessment of diastolic function. Both the left ventricle and the left atrium were tracked simultaneously using speckle-tracking echocardiography (STE) for measuring simultaneous changes in left atrial and ventricular volumes, volume rates, longitudinal strains, and strain rates. Patients in the validation group also underwent invasive measurements of pulmonary capillary wedge pressure and LV end diastolic pressure immediately after echocardiography. The similarity between STE and conventional 2-dimensional and Doppler methods of diastolic function was investigated in both the exploratory and validation cohorts. RESULTS: STE demonstrated strong correlations with the conventional indices and independently clustered the patients into 3 groups with conventional measurements verifying increasing severity of diastolic dysfunction and LV filling pressures. A multivariable linear regression model also allowed estimation of E/e' and pulmonary capillary wedge pressure by STE in the validation cohort. CONCLUSIONS: Tracking deformation of the left-sided cardiac chambers from routine cardiac ultrasound images provides accurate information for Doppler-independent phenotypic characterization of LV diastolic function and noninvasive assessment of LV filling pressures.

Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction: Association With Exercise Capacity, Left Ventricular Filling Pressures, Natriuretic Peptides, and Left Atrial Volume.

OBJECTIVES: This study sought to study the association of atrial fibrillation (AF) with exercise capacity, left ventricular filling pressure, natriuretic peptides, and left atrial size in heart failure with preserved ejection fraction (HFpEF). BACKGROUND: The diagnosis of HFpEF in patients with AF remains a challenge because both contribute to impaired exercise capacity, and increased natriuretic peptides and left atrial volume. METHODS: We studied 94 patients with symptomatic heart failure and left ventricular ejection fractions ≥45% using treadmill cardiopulmonary exercise testing and right- and/or left-sided cardiac catheterization with simultaneous echocardiography. RESULTS: During catheterization, 62 patients were in sinus rhythm, and 32 patients had AF. There were no significant differences in age, sex, body size, comorbidities, or medications between groups; however, patients with AF had lower peak oxygen consumption (VO2) compared with those with sinus rhythm (10.8 ± 3.1 ml/min/kg vs. 13.5 ± 3.8 ml/min/kg; p = 0.002). Median (25th to 75th percentile) N-terminal pro-B-type natriuretic peptide (NT-proBNP) was higher in AF versus sinus rhythm (1,689; 851 to 2,637 pg/ml vs. 490; 272 to 1,019 pg/ml; p < 0.0001). Left atrial volume index (LAVI) was higher in AF than sinus rhythm (57.8 ± 17.0 ml/m2 vs. 42.5 ± 15.1 ml/m2; p = 0.001). Invasive hemodynamics showed higher mean pulmonary capillary wedge pressure (PCWP) (19.9 ± 3.7 vs. 15.2 ± 6.8) in AF versus sinus rhythm (all p < 0.001), with a trend toward higher left ventricular end-diastolic pressure (17.7 ± 3.0 mm Hg vs. 15.7 ± 6.9 mm Hg; p = 0.06). After adjusting for clinical covariates and mean PCWP, AF remained associated with reduced peak VO2 increased log NT-proBNP, and enlarged LAVI (all p ≤0.005). CONCLUSIONS: AF is independently associated with greater exertional intolerance, natriuretic peptide elevation, and left atrial remodeling in HFpEF. These data support the application of different thresholds of NT-proBNP and LAVI for the diagnosis of HFpEF in the presence of AF versus the absence of AF.

Echocardiographic correlates of left ventricular filling pressures and acute cardio-renal syndrome in ST segment elevation myocardial infarction patients.

OBJECTIVE: Increased transmitral flow velocity (E) to the early mitral annulus velocity (e') ratio (E/e'), signifying increased cardiac filling pressure, was previously found to be associated with deterioration of renal function in patients with congestive heart failure. No study, however, included patients with acute myocardial ischemia. We hypothesized that elevated E/e' ratio would be associated with an increased risk of acute kidney injury (AKI) in ST elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). STUDY DESIGN AND METHODS: We conducted a retrospective study of 804 consecutive STEMI patients between June 2012 and December 2015 who underwent primary PCI and had a comprehensive echocardiographic examination performed within 72 h of hospital admission. Patients were stratified according to E/e' ratio above and ≤15, and assessed for AKI using the KDIGO criteria, defined as either a serum creatinine rise >0.3 mg/dl, or an increase in serum creatinine ≥1.5 times baseline. RESULTS: Patients with E/e' ratio >15 had lower left ventricular (LV) ejection fraction, higher systolic pulmonary artery pressures, as well as right atrial pressures, and demonstrated worse in-hospital outcomes. Patients with E/e' ratio >15 had more AKI complicating STEMI (27 vs. 7 %; p < 0.001). In multivariate logistic regression model, E/e' ratio >15 was independently associated with AKI (OR = 1.87, 95 % CI 0.99-3.52; p = 0.05). Other variables associated with AKI included diabetes, LV ejection fraction, and glomerular filtration rate. CONCLUSIONS: Among STEMI patients undergoing primary PCI, the early E/e' ratio >15 was associated with increased risk for AKI.

Longitudinal strain of left ventricular basal segments and E/e' ratio differentiate primary cardiac amyloidosis at presentation from hypertensive hypertrophy: an automated function imaging study.

BACKGROUND: Longitudinal strain is an early marker of left ventricular (LV) dysfunction in several cardiac diseases. Our aim was to differentiate cardiac amyloidosis (CA) at diagnosis from hypertensive LV hypertrophy (LVH) by analysis of longitudinal myocardial deformation. METHODS: Thirty healthy controls (C), 30 newly diagnosed, never treated hypertensives with LVH (H-LVH), and 33 patients with CA at diagnosis underwent echo Doppler including speckle tracking-based automated function imaging (AFI). Averaged peak systolic global longitudinal strain (GLS, 18 segments) and basal, middle, and apical longitudinal strain (BLS, MLS, and ALS, respectively, six segments each) were calculated. RESULTS: Left ventricular mass index, relative wall thickness, and ejection fraction did not differ between H-LVH and CA. E/e' ratio was higher in CA than in H-LVH (P<.001) and C (P<.0001). GLS was lower in CA than in C (P<.0001), without difference with H-LVH. ALS did not differ among the three groups, MLS was significantly lower in both CA and H-LVH than in C but BLS was lower in CA compared to both H-LVH and C (both P<.0001). In the pooled population, E/e' was independently associated with BLS (ß=-0.54, P<.0001). At receiver operating curve analysis, CA was predicted by BLS≤-11.3% (sensitivity=63.3%, specificity=100%) and E/e'≥12.3 (sensitivity=69.7%, specificity=83.3%). The best AUC (=0.819) was obtained by the combination E/e'+BLS. CONCLUSIONS: Our findings highlight a real difference of E/e' ratio and longitudinal strain of LV basal segments between hypertensive LVH and CA, which could be used to differentiate the two diseases.

Predictive value of E/A and E/E' Doppler indexes for cardiac events in heart transplant recipients.

BACKGROUND: Doppler-derived indexes associated with high left ventricular filling pressures are risk factors for cardiac events in various populations. The aim of this study was to evaluate the predictive value of two of these Doppler indexes during the long-term follow-up of heart transplantation. METHODS AND RESULTS: In this cohort study, we measured E/A ratio combining early filling velocity (E) with late filling velocity (A) and E/E' ratio combining E wave with relaxation velocity on tissue doppler (E') in 122 transplant heart recipients, 6.9±5.9 years after transplantation. The patients were followed for 97±32 months after Doppler measurements. We found an E/A>2 in 68 patients and an E/E'>15 in 23 patients. Forty patients had a cardiac event (cardiac death, retransplantation, acute coronary events, hospitalization for heart failure, treated acute rejection episodes, and coronary revascularization procedures) during the follow-up. In multivariate analysis, E/A and E/E' were significantly associated with cardiac events (hazard ratio 2.2, 95% CI: 1.1-4.4; P=.02 and hazard ratio 2.3, 95% CI: 1.1-4.8; P=.02, respectively). E/E', E/A, and significant coronary stenoses were the strongest predictors of cardiac events. CONCLUSIONS: E/A and E/E' Doppler indexes may be used to predict cardiac events during the long-term follow-up of heart transplant recipients.

Adverse Cardiac Events and the Impaired Relaxation Left Ventricular Filling Pattern.

BACKGROUND: Increasing diastolic dysfunction (DD) grade is associated with increased heart failure (HF). Patients with preserved ejection fractions and grade 1 DD may have left atrial dilatation, e' < 8 cm/sec, increased left ventricular (LV) mass, or variable E/e' ratios. The aim of this study was to test the hypothesis that LV hypertrophy or E/e' ratio > 8 may be associated with a greater incidence of HF. METHODS: Two hundred twelve patients with grade 1 DD and ejection fractions > 50% were retrospectively studied. Group 1 comprised 108 patients with E/A ratios < 0.8, without LV hypertrophy, e' < 8 cm/sec, and E/e' ratios < 8. Group 2 comprised 104 patients with LV hypertrophy or E/e' ratios > 8. Patients with incident HF and valvular or coronary disease were excluded. Using two-dimensional Doppler echocardiography, LV and left atrial volumes and transmitral spectral and tissue Doppler were analyzed. Medical records were examined for laboratory data, HF admissions, and all-cause mortality from 2004 to 2012. RESULTS: Despite similar ejection fractions, patients in group 2 had greater LV and left atrial volumes, LV mass index values, and E/e' ratios (P < .01 for all). HF incidence was greater in group 2 (30 vs 4, P < .001). Combined HF or all-cause mortality was greater in group 2 (46 vs 14, P < .001). Multivariate analysis revealed that HF was associated with E/e' ratio (P < .0001), systolic blood pressure (P = .0123), and LV mass index (P = .042). Combined HF or all-cause mortality was associated with E/e' ratio (P < .0001), LV mass index (P = .009), and lower calcium channel blocker use (P = .0011). CONCLUSIONS: HF alone or HF and all-cause mortality were increased in patients with grade 1 DD in the presence of LV hypertrophy or elevated LV filling pressures.

Correlation of Left Atrial Strain and Doppler Measurements with Invasive Measurement of Left Ventricular End-Diastolic Pressure in Patients Stratified for Different Values of Ejection Fraction.

BACKGROUND: This study aimed at exploring the correlation of left atrial longitudinal function by speckle tracking echocardiography (left atrial strain) and Doppler measurements (E/E' ratio) with direct measurements of left ventricular (LV) end-diastolic pressure (LVEDP) in patients stratified for different values of ejection fraction. METHODS: The study population was 80 stable patients with sinus rhythm undergoing cardiac catheterization. This population was selected in order to have four groups of 20 patients each with different LV ejection fraction (>55%, 45-54%, 30-44%, and <30%). LVEDP was obtained during cardiac catheterization; peak atrial longitudinal strain (PALS) and mean E/E' ratio were measured in all subjects. RESULTS: Similar correlations with LVEDP of global PALS and E/E' ratio were recorded in patients with preserved (r = -0.79 vs. r = 0.72, respectively; P < 0.0001 for both) or mildly reduced ejection fraction (r = -0.75 vs. r = 0.73, respectively; P < 0.0001 for both). A closer correlation of global PALS compared to E/E' ratio was evident in patients with moderate (r = -0.78 P < 0.0001; vs. r = 0.47 P = 0.01, respectively) and severe reduction (r = -0.74 P < 0.0001; vs. r = 0.19 ns, respectively) of LV ejection fraction. In multivariate analysis of all measurements, global PALS emerged as a determinant of the LVEDP, independent on other confounding factors and, with the cutoff value of 18.0% presented the best diagnostic accuracy to predict a LVDP above 12 mmHg (AUC 0.87). CONCLUSIONS: In patients with preserved or mildly reduced LV ejection fraction, global PALS and mean E/E' ratio presented good correlations with LVEDP. In patients with moderate or severe reduction of ejection fraction, E/E' ratio correlated poorly with invasively obtained LV filling pressures. Global PALS provided an overall better estimation of LV filling pressures.