Ratio Of Early Mitral Inflow Research Articles

Abnormal inter-ventricular diastolic mechanical delay in patients with ST-segment elevation myocardial infarction

BackgroundThis study aimed to investigate the ventricular mechanical relaxation pattern and its clinical influence in patients with ST-segment elevation myocardial infarction (STEMI).MethodsEchocardiography was performed to measure mitral and tricuspid diastolic opening times. Left ventricular diastolic mechanical delay (LVMDd) was defined as diastolic filling of the right ventricle earlier than that of the left ventricle, and right ventricular diastolic mechanical delay (RVMDd) was defined as the right ventricular diastolic filling later than left ventricular filling.ResultsAmong 152 patients with STEMI, 100 (65.8%) had LVMDd, and 47 (30.9%) had RVMDd. In-hospital complications were significantly increased in patients with RVMDd (61.6% vs. 41.0%, P = 0.017). Those with RVMDd exhibited significantly lower left ventricular global longitudinal strain (11.7 ± 4.1% vs. 13.2 ± 4.0%, P = 0.035), global work index (913.8 ± 365.9 vs. 1098.9 ± 358.8 mmHg%, P = 0.005) and global constructive work (1218.6 ± 392.8 vs. 1393.7 ± 432.7 mmHg%, P = 0.021). Mitral deceleration time significantly decreased (127.4 ± 33.5 vs. 145.6 ± 41.7 ms, P = 0.012), and the ratio of early mitral inflow to early mitral annular velocity (E/E’) significantly increased [13.0(11.0–20.0) vs. 11.9(9.3–14.3), P = 0.006] in the RVMDd group. Logistic regression analysis showed that age (odds ratio [OR]:0.920; P = 0.001), brain natriuretic peptide level (OR: 1.1002; P = 0.036) and mitral E/E’ (OR: 1.187; P = 0.003) were independently associated with RVMDd.ConclusionsDelayed right ventricular filling is related to more severe left ventricular systolic and diastolic dysfunction in STEMI patients. More attention should be paid to patients with RVMDd to prevent adverse events during hospitalization.

Prognostic relevance of left atrial function and stiffness in heart failure with preserved ejection fraction patients with and without diabetes mellitus.

BackgroundAlthough the left atrium (LA) plays a key role in the pathophysiology and disease progression of heart failure with preserved ejection fraction (HFpEF), the impact of type 2 diabetes mellitus (T2DM) on LA function and stiffness in HFpEF patients remains unclear. Furthermore, the prognostic value of different phases of LA function and stiffness is less well-established in HFpEF patients.MethodsThis study prospectively enrolled 164 HFpEF patients who were in sinus rhythm at the time of echocardiography, including 61 (37%) HFpEF patients with T2DM. LA reservoir, conduit, and pump function were assessed using two-dimensional volume indices and speckle tracking echocardiography. The LA stiffness was calculated as the ratio of early mitral inflow velocity-to-early annular tissue velocity (E/e’) and LA reservoir function. The primary end point was a combined outcome of heart failure hospitalization or death.ResultsLeft atrium reservoir function [measured by peak LA strain (LAS-peak)] and LA pump function (measured by LAS-active) remained significantly lower in the HFpEF patients with T2DM compared with those without T2DM, even after adjustment for potential confounders. In addition, the LA stiffness of HFpEF patients with T2DM was higher than those without T2DM. After a median follow-up of 13.7 months, 46 patients (28.1%) reached the composite end point. LAS-peak (hazard ratios: 0.88; 95% confidence interval: 0.81–0.95; P = 0.001) was significantly associated with the risk of heart failure hospitalization or death after adjusting for demographic and clinical characteristics, LV global longitudinal strain, E/e’, and LA volume index. In contrast, other LA function and stiffness parameters did not independently predict the risk of adverse events. Kaplan-Meier analysis showed that HFpEF patients with T2DM and low LAS-peak (<27.2%) had a significantly increased risk of heart failure-related hospitalization or death (log-rank P < 0.001).ConclusionLeft atrium reservoir and pump function are impaired, whereas LA stiffness is increased in HFpEF patients with T2DM compared with those without T2DM. LAS-peak is a powerful predictor of adverse clinical outcomes and may be crucial for risk stratification in HFpEF patients with and without T2DM.

Left Atrial Stiffness Index Independently Predicts Exercise Intolerance and Quality of Life in Older, Obese Patients With Heart Failure With Preserved Ejection Fraction

BackgroundHeart failure with preserved ejection fraction (HFpEF) is the fastest growing form of HF and is associated with high morbidity and mortality. The primary chronic symptom in HFpEF is exercise intolerance, associated with reduced quality of life. Emerging evidence implicates left atrial (LA) dysfunction as an important pathophysiologic mechanism. Here we extend prior observations by relating LA dysfunction to peak oxygen uptake (peak VO2), physical function (distance walked in 6 minutes [6MWD]) and quality of life (Kansas City Cardiomyopathy Questionnaire). Methods and ResultsWe compared 75 older, obese, patients with HFpEF with 53 healthy age-matched controls. LA strain was assessed by magnetic resonance cine imaging using feature tracking. LA function was defined according to its 3 distinct phases, with the LA serving as a reservoir during systole, as a conduit during early diastole, and as a booster pump at the end of diastole. The LA stiffness index was calculated as the ratio of early mitral inflow velocity-to-early annular tissue velocity (E/e’, by Doppler ultrasound examination) and LA reservoir strain. HFpEF had a decreased reservoir strain (16.4 ± 4.4% vs 18.2 ± 3.5%, P = .018), lower conduit strain (7.7 ± 3.3% vs 9.1 ± 3.4%, P = .028), and increased stiffness index (0.86 ± 0.39 vs 0.53 ± 0.18, P < .001), as well as decreased peak VO2, 6MWD, and lower quality of life. Increased LA stiffness was independently associated with impaired peak VO2 (β = 9.0 ± 1.6, P < .001), 6MWD (β = 117 ± 22, P = .003), and Kansas City Cardiomyopathy Questionnaire score (β = –23 ± 5, P = .001), even after adjusting for clinical covariates. Conclusions: LA stiffness is independently associated with impaired exercise tolerance and quality of life and may be an important therapeutic target in obese HFpEF. RegistrationNCT00959660

Estrogen Modulates the Differential Expression of Cardiac Myocyte Chymase Isoforms and Diastolic Function

Background and objectiveCardiac angiotensin II (Ang II) is involved in the diastolic dysfunction in postmenopausal women. Chymases, a family of serine proteases with chymotryptic activity, play a significant role in cardiac Ang II formation from its substrate Ang‐(1–12) in both human and rodent models. While human tissue expresses only the α‐form of chymase, α‐ and β‐forms exist in rodents. Five of the ten rat mast cell proteases (rMCP‐1–5) display chymase activity, and rats express predominantly the β‐chymase isoforms. This study was designed to assess the differences in enzymatic activity among these rMCP isoforms in Ang II formation, particularly in the cardiomyocyte (CM), and the effects of estrogen status on MCP gene expression and activities in female rat models.Methods and resultsUsing conventional polymerase chain reaction (PCR) (Fig. 1A), real‐time PCR (Fig. 1B) and DNA sequencing (Fig. 1C), we demonstrated that MCP‐1, MCP‐2, MCP‐4, and MCP‐5 mRNAs are expressed in the CM of both spontaneously hypertensive rats (SHR) and normotensive Wistar‐Kyoto rats (WKY). While rMCP‐1 and rMCP‐5 gene transcripts were higher than other isoforms in both rat strains, WKY CM exhibits higher levels of rMCP‐1 and rMCP‐5 mRNAs compared to the SHR CM (Fig. 2). Ovariectomy (OVX) increased the expression of rMCP‐1 and rMCP‐5 mRNAs in WKY. In SHR, OVX was associated with a blunted increase in rMCP‐1 mRNA compared to OVX normotensive WKY. Chymase activity, measured by HPLC as Ang II formation from Ang‐(1–12), significantly correlated with rMCP‐1 and rMCP‐5 mRNA expression in both rat strains. Both rMCP‐1 and rMCP‐5 mRNA expressions were positively correlated with progressive diastolic dysfunction (increasing the ratio of early mitral inflow velocity‐to‐early mitral annular velocity, E/e′) and increases in left ventricular internal diameter end diastole.ConclusionThese data show rMCP‐1 and rMCP‐5 as the Ang II forming chymase isoforms participating in diastolic dysfunction due to ovariectomy in rodents.Support or Funding InformationThis work was funded by grants from the National Heart Lung and Blood Institute (CMF and LG) P01‐HL051952 and the National Institute on Aging (LG) AG033727 of the National Institute of Health.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Estrogen modulates the differential expression of cardiac myocyte chymase isoforms and diastolic function.

Chymases, a family of serine proteases with chymotryptic activity, play a significant role in cardiac angiotensin II (Ang II) formation from its substrate Ang-(1-12) in both human and rodent models. No studies, to date, have assessed the differences in enzymatic activity among these isoforms in Ang II formation, particularly in the cardiomyocyte (CM). Using PCR and DNA sequencing, we demonstrated that MCP-1, MCP-2, MCP-4, and MCP-5 mRNAs are expressed in the CM of both spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). While rMCP-1 and rMCP-5 gene transcripts were higher than that of other isoforms in both rat strains, WKY CM exhibits higher levels of rMCP-1 and rMCP-5 mRNAs compared to the SHR CM. Ovariectomy (OVX) increased the expression of rMCP-1 and rMCP-5 mRNAs in WKY. In SHR, OVX was associated with a blunted increase in rMCP-1 mRNA compared to OVX normotensive WKY. Chymase activity, measured as Ang II formation from Ang-(1-12), significantly correlated with rMCP-1 and rMCP-5 mRNA expression in both rat strains. Both rMCP-1 and rMCP-5 mRNA expressions were positively correlated with progressive diastolic dysfunction (increasing the ratio of early mitral inflow velocity-to-early mitral annular velocity, E/e') and expanding chamber dimensions or increasing left ventricular internal diameter end diastole. These data show rMCP-1 and rMCP-5 as the Ang II forming chymase isoforms participating in the loss of normal cardiac function due to OVX in rodents.

IGFBP7 (Insulin-Like Growth Factor-Binding Protein-7) and Neprilysin Inhibition in Patients With Heart Failure.

Increased activity of IGFBP7 (insulin-like growth factor-binding protein-7) is associated with cellular senescence, tissue aging, and obesity. IGFBP7 may be related to heart failure with preserved ejection fraction, a disease of elderly obese people. In a subset of patients with heart failure with preserved ejection fraction (N=228) randomized to receive sacubitril/valsartan versus valsartan, IGFBP7 concentrations were measured at baseline, 12 weeks, and 36 weeks. Patient characteristics and echocardiographic measures including left atrial (LA) size and volume, ratio of early mitral inflow velocity/annular diastolic velocity, and ratio of early diastole/peak late diastolic velocity were assessed as a function of IGFBP7 concentration. Effect of sacubitril/valsartan on IGFBP7 concentrations was analyzed. With increasing baseline IGFBP7 quartiles, LA size and LA volume index (LAVi) were higher (both P<0.001); modest association between IGFBP7 and higher early mitral inflow velocity/annular diastolic velocity ( P=0.03) and early diastole/peak late diastolic velocity ratio ( P=0.04) was also seen. IGFBP7 concentrations were higher in those with LAVi ≥34 mL/m2 compared with lower LAVi at all time points (all P<0.01). IGFBP7 independently predicted LAVi at baseline even in the presence of NT-proBNP (N-terminal pro-B-type natriuretic peptide) concentrations; highest LAVi was seen in those with elevation in both biomarkers. Treatment with sacubitril/valsartan resulted in lower IGFBP7 concentrations over 36 weeks compared with valsartan (adjusted treatment effect, -7%; P<0.001). Among patients with heart failure with preserved ejection fraction, concentrations of the cellular senescence biomarker IGFBP7 were associated with abnormalities in diastolic filling and LA dilation. Treatment with sacubitril/valsartan resulted in lower IGFBP7 concentrations compared with valsartan. URL: https://www.clinicaltrials.gov . Unique identifier: NCT00887588.

Correlation with invasive left ventricular filling pressures and prognostic relevance of the echocardiographic diastolic parameters used in the 2016 ESC heart failure guidelines and in the 2016 ASE/EACVI recommendations: a systematic review in patients with heart failure with preserved ejection fraction.

Five echocardiographic parameters-left atrial volume index, left ventricular mass index, tricuspid regurgitation velocity, myocardial tissue velocity, and the ratio of early mitral inflow to tissue velocity of the mitral annulus (E/e')-are recommended in both the current European Society of Cardiology heart failure guidelines and the American Society of Echocardiography/European Association of Cardiovascular Imaging recommendations for the evaluation of left ventricular diastolic function. We aimed to perform a systematic review of these echocardiographic parameters at resting conditions for their correlation with left ventricular filling pressures in patients with heart failure with preserved ejection fraction (HFpEF). In addition, the prognostic value of these parameters was assessed. Nine studies reported the correlation between echocardiography and invasive haemodynamics, and 18 papers reported on the prognostic value of echocardiography in HFpEF. Among the parameters, most data were reported for E/e'. The pooled correlation coefficient r was 0.56 for the relation between E/e' and invasively measured filling pressures. Combined weighted-mean meta-analysis of prognostic studies resulted in a hazard ratio of 1.05 (95% confidence interval 1.03-1.06) per unit increase in E/e' for the combined outcome of all-cause mortality and cardiovascular hospitalization. The other echocardiographic parameters, when taken individually, had similar or lower association with prognosis. Only a small number of studies validated the use of echocardiographic parameters at rest in patients with HFpEF. The best established parameter appears to be E/e', but the existing data only show modest correlations of E/e' with invasive filling pressures and outcomes in HFpEF.

Usefulness of Diastolic Strain Measurements in Predicting Elevated Left Ventricular Filling Pressure and Risk of Rejection or Coronary Artery Vasculopathy in Pediatric Heart Transplant Recipients

In pediatric heart transplant recipients, elevated pulmonary capillary wedge pressure (PCWP) is associated with rejection and coronary artery vasculopathy. This study aimed to evaluate which echocardiographic parameters track changes in PCWP and predict adverse outcomes (rejection or coronary artery vasculopathy). This prospective single-center study enrolled 49 patients (median 11.4 years old, interquartile range 7.4 to 16.5) at time of cardiac catheterization and echocardiography. Median follow-up was 2.4 years (range 1.2 to 3.1 years), with serial testing per clinical protocol. Ratio of early mitral inflow to annular velocity (E/E'), left atrial (LA) distensibility, peak LA systolic strain, E/left ventricular (LV) diastolic strain, and E/LV diastolic strain rate were measured from echocardiograms. Increase in PCWP ≥3 mm Hg was associated with changes in LA distensibility, E/E', and E/LV diastolic strain, with highest area under the receiver operating characteristic curve for E/LV diastolic strain (0.76). In 9 patients who subsequently developed rejection or coronary artery vasculopathy, E/LV diastolic strain rate at baseline differed from patients without events (median 57.0 vs 43.6, p = 0.02). On serial studies, only change in LV ejection fraction differed in patients with events (median -10% vs -1%, p = 0.01); decrease in LV ejection fraction of -19% had a specificity of 100% and sensitivity of 44%. In conclusion, LV diastolic strain and strain rate measurements can track changes in PCWP and identify patients at risk for subsequent rejection or coronary artery vasculopathy. Further studies are necessary to confirm these data in a larger cohort.

Impact of Left Anterior Line on Left Atrial Appendage Contractility in Patients Who Underwent Catheter Ablation for Chronic Atrial Fibrillation

Left anterior line (LAL) has been used as a substitute for mitral isthmus line for catheter ablation of chronic atrial fibrillation (AF). However, it results in left anterolateral conduction delay and might affect left atrial (LA) contractility. We aimed to investigate whether LAL decreases LA appendage function. This study included 46 patients (30 men, mean age 58 ± 9 years, group 1) with persistent AF who underwent catheter ablation including LAL. Thirty patients with paroxysmal AF who received no additional LA ablation were compared as control group (21 males, mean age 56 ± 8 years, group 2). Transthoracic and transesophageal echocardiography with Doppler tissue imaging was performed in sinus rhythm before and after the ablation. We compared the following variables: (1) E/A ratio of the mitral flow velocity, (2) ratio of early mitral inflow and mitral septal annulus velocity (E/Em), (3) peak velocity of appendage outflow (ApVmax), and (4) time delay from QRS onset to appendage outflow (TDqa). LA diameter was significantly reduced after ablation in both groups. In group 1, parameters for diastolic function (E/A ratio, 1.7 ± 0.5 vs 2.0 ± 0.6, P = 0.197; E/Em, 11.7 ± 4.8 vs 11.6 ± 5.1, P = 0.883) and appendage flow (ApVmax, 55.2 ± 19.9 cm/s vs 50.3 ± 19.3 cm/s, P = 0.203; TDqa, -77.3 ± 30.1 ms vs -66.1 ± 60.8 ms, P = 0.265) did not change significantly after ablation. Changes of ApVmax and TDqa after ablation were not significantly different between two groups (P = 0.409 and P = 0.195, respectively). LAL ablation did not aggravate mitral flow pattern or change appendage outflow. LAL could be used without concern over worsening LA diastolic and appendage function.

The validity of a global tissue Doppler index in estimating left ventricular end-diastolic pressure in patients with coronary artery disease

Background The left ventricular end diastolic pressure (LVEDP) is an important parameter in cardiac patients. There are few data on adding tissue Doppler derived mitral annular peak systolic velocity (S′) wave to the ratio of early mitral inflow to mitral annular velocity (E/E′) for the estimation of left ventricular end diastolic pressure (LVEDP) in patients with preserved LV ejection fraction. Objectives To assess the validity of E/(E′A ∼ S′) in estimating LVEDP in patients with CAD and intermediate E/E′. Methods Sixty-five subjects underwent echocardiography and TDI of the mitral annulus in less than 30 min of cardiac catheterization. Echocardiographic variables including E/E′ and E/(E′A ∼ S′) were compared to invasively measured LVEDP. Results Based on coronary angriography, 49 subjects showed significant CAD (group I) while 16 subjects showed no evidence of CAD (control group). The E/E′ and the E/(E′X S′) were significantly higher in CAD patients than in the control group ( P r = 0.785, P r = 0.274, P > 0.05). ROC analysis yielded an optimal E/(E′A ∼ S′) cutoff value of 1.43 for prediction of LVEDP >12 mmHg with a sensitivity of 90.9%, a specificity of 57.1%, a positive predictive value of 76.9% and a negative predictive value of 80.0% (AUC 0.88, 95% CI 0.71–1.00, P 12 mmHg with a sensitivity of 72.7%, a specificity of 28.6%, a positive predictive value of 61.5% and a negative predictive value of 40.0% (AUC 0.68, 95% CI 0.44–0.93, P > 0.05). Conclusions E/(E′A ∼ S′) correlates well with LVEDP and can be used as a simple andaccurate estimate ofLVEDP in coronary artery disease patients with intermediate E/E′.

Do Additional Echocardiographic Variables Increase the Accuracy of E/e′ for Predicting Left Ventricular Filling Pressure in Normal Ejection Fraction? An Echocardiographic and Invasive Hemodynamic Study

There are few data on adding left atrial volume index (LAVi) or pulmonary artery systolic pressure (PAP) to the ratio of early mitral inflow to mitral annular velocity (E/e') for the estimation of left ventricular (LV) filling pressure in patients with preserved LV ejection fractions (LVEFs) (>50%). Patients underwent echocardiography within 20 minutes of cardiac catheterization. Echocardiographic variables were compared with invasively measured LV preatrial contraction pressure (pre-A). Of the 122 patients studied (mean age, 55 +/- 9 years; mean LVEF, 61 +/- 6%), 67 (55%) were women, 108 (88%) had hypertension, and 79 (65%) had significant coronary artery disease at catheterization. E/e' was significantly correlated with pre-A (R = 0.63, P < .0001) compared with LAVi (R = 0.49, P < .001) and PAP (R = 0.48, P < .001). E/e' > 13 had sensitivity of 70% and specificity of 93% (area under the curve [AUC], 0.82; P < .0001), LAVi > 31 mL/m2 had sensitivity of 78% and specificity of 76% (AUC, 0.80, P < .001), and PAP > 28 mm Hg had sensitivity of 80% and specificity of 64% for pre-A > 15 mm Hg (AUC, 0.77, P < .001). Adding LAVi >31 mL/m2 for E/e' = 8 to 13 significantly increased the accuracy of E/e' > 13 alone (sensitivity, 87%; specificity, 88%; AUC, 0.89; P = .01 for comparison). However, adding PAP > 28 mm Hg for E/e' = 8 to 13 did not significantly increase the accuracy of E/e' > 13 alone (AUC, 0.82; sensitivity, 82%; specificity, 72%; P = NS for comparison). In patients with preserved LVEFs, adding LAVi > 31 mL/m2 to E/e' (when E/e' was in the gray zone, but not when E/e' was >13) significantly increased the accuracy of E/e' alone for the estimation of LV filling pressure. These data support the notion of using several, rather than any single, Doppler echocardiographic parameter for the accurate assessment of LV diastolic function.

Tissue Doppler imaging provides incremental prognostic value in patients with systemic hypertension and left ventricular hypertrophy

We sought to determine the prognostic value of left ventricular (LV) mitral annular velocities measured by tissue Doppler imaging (TDI) in hypertensive patients with echocardiographic evidence of LV hypertrophy. Echo LV hypertrophy and LV geometry provide additional predictive value of all-cause mortality beyond traditional cardiovascular risk factors. Limited data exist regarding the predictive value of TDI velocities for cardiovascular risk stratification in treated hypertensive patients. Two-dimensional and Doppler echocardiograms were obtained in 252 consecutive subjects, including 174 subjects with systemic hypertension and 78 age-matched normal subjects. The end point was cardiac death in subsequent median follow-up of 19 months. Nineteen patients (7.54%) died of cardiac causes. The TDI mitral annulus systolic velocity and the early diastolic mitral annular velocity (Em) were significantly lower in the non-survivors (all P < 0.001). The pseudonormal (PN) or restrictive filling pattern (RFP) was associated with cardiac mortality. The other parameters associated with cardiac mortality were LV ejection fraction, LV mass index, inter-ventricular septal wall thickness in diastole and the ratio of early mitral inflow to early myocardial velocity. In multivariate analysis, Em, inter-ventricular septal wall thickness in diastole and either PN or RFP were the strongest predictors. The addition of Em < 3.5 cm/s significantly improved the outcome of a model that contained clinical risk factors, inter-ventricular septal wall thickness in diastole > 1.4 cm and either PN or RFP (P = 0.043). Early diastolic mitral annulus velocity measured by TDI provides prognostic information, incremental to clinical data and standard echocardiographic variables, for risk stratification of hypertensive patients under treatment.

Mitral annulus velocity in the estimation of left ventricular filling pressure: Prospective study in 200 patients

The ratio of early mitral inflow to early mitral annular velocity (E/E′) was suggested as a useful index in the estimation of left ventricular filling pressure. This study was performed to validate the clinical usefulness of E/E′ ratio in a large number of patients. Simultaneous left ventricular pressure measurements and Doppler examinations were performed in 200 consecutive patients at the cardiac catheterization laboratory. The E/E′ ratio correlated well with pre-A-wave pressure (r = 0.74, P <.001), and the correlation was not dependent on the left ventricular systolic function (ejection fraction [EF] ≥50%: r = 0.74, P <.001 versus EF <50%: r = 0.70, P <.001). The E/E′ ratio of ≥9 best discriminated elevated (<12 mm Hg) from normal left ventricular pre-A pressure with a sensitivity of 81% and a specificity of 80%. Our study results also showed that quantitative estimation of left ventricular pre-A pressure could be suggested by the simplified equation of pre-A pressure = E/E′ + 4 with reasonable accuracy. (J Am Soc Echocardiogr 2000;13:980-5.)